First, PKU causes and symptoms
Dr.Folling Norway in 1934 at familial mental retardation found in the urine of patients with special triteness Taste
, Was later learned the substances are phenylketonuria (phenylpyruvic acid), officially named in 1937 for the benzene
Ketone urine disease (phenylketonuria; PKU). Phenylketonuria is an autosomal recessive genetic diseases, the main
If the body because of phenylalanine (phenylalanine; Phe) hydroxylation (hydroxylation) into tyrosine (tyrosine
; Tyr) of the metabolic pathway machine caused by impaired innate metabolic disorders. Currently known to have five different fermentation
Lack of pigment would cause such a metabolic drive impaired; these include: phenylalanine hydroxylation enzyme (phenylalanine
hydroxylase; PAH), guanine nucleoside triphosphate cyclohydrolase enzyme hydrolysis (Gtp cyclohydrolase I;
GTPCHI), C dione tetrahydro biopterin synthase (6-pyruvoyl tetrahydropterin synthase;
PTPS), HD-acridine Dihydroartemisinin reductase (dihydropteridine reductase; DHPR) and methyl amine neopterin
Dehydration enzyme (pterin-4 -carbinolamine dehydratase; PCD). Different depending on the lack of will
Have different clinical symptoms and diagnostic methods, and its treatment methods are also different.
The first enzyme phenylalanine hydroxylation (PAH) can cause a lack of the most common typical phenylketonuria. Its clinical
Show symptoms of yellow hair, pale skin dry and intellectual disability sequelae. According to literature reports, the European
PKU patients with the United States about 98 ~ 99% for this type, its incidence is about one ten thousandth, but there is a lot of areas
And racial differences. Domestic screening results showed that 870,000 newborns, PKU incidence of approximately 34,000
Thousandth, of which only about 70 ~ 80% typical phenylketonuria patients.
The second to fourth result in the lack of hydroxylation of phenylalanine into tyrosine when necessary auxiliary enzymes tetrahydro Health
Biopterin (tetrahydrobiopterin; BH4) lack. Their clinical symptoms apart from the typical symptoms of phenylketonuria and some outside
, There are serious neurological symptoms (such as convulsions), growth retardation, easy infection.
Fifth, although the lack of enzymes may also result in ancillary tetrahydro Health neopterin deficiencies, but the clinical symptoms of mild, may
Do not need treatment. PKU patients in China, about 20% ~ 30% for lack of tetrahydro Health neopterin type, with the West Country
The results to differ materially, especially in the differential diagnosis necessary in order to adopt the correct method of treatment.
Second, treatment of phenylketonuria
To prevent the occurrence of sequelae of PKU, except to be the right remedy, and the sooner the better therapeutic effect. Root
According to foreign literature, the treatment of patients at one month, the average IQ of 95, one to two months before administration
Treatment of patients, with an average IQ of 85; and advanced medical treatment or treatment, the average IQ was 53-45.
According to the experience of domestic and foreign literature, BH4 treatment type lack of a good prognosis, especially neurological symptoms
Control and the growth and development, if that is during the neonatal period for treatment, their IQ can be reached normal subscript
Prospective.
PKU patients with various types of treatment are as follows:
(A) typical PKU: given the low phenylalanine diet control, so that the blood phenylalanine concentration maintained at 4-8
mg / dL, but we must also consider the protein, calories, such as balanced nutrition to maintain the patient's normal growth. Drink
Fresh control the longer the better, at least to maintain the six-year-old. Female cases of child-bearing age should be continued until after
In order to avoid future occurrence of maternal phenylketonuria (maternal PKU), congenital disabilities caused by the next generation of children
Generated.
(B) Health Des tetrahydro biopterin synthesis lack of type (guanine nucleoside triphosphate cyclohydrolase enzyme hydrolysis, C iv dione
Hydrogen neopterin synthesis enzyme): given BH4 (1-5 mg / kg / day), so that the blood phenylalanine concentration of at least dimension
Holders at the following 4mg/dL. Because patients have neurological symptoms, have to supplement the central nervous system conduction precursors
Quality, L-dopa (5-15 mg / kg / day) and 5-hydroxy tryptophan (4-10 mg / kg / day),
carbidopa (1-2mg/kg/day), nerve conduction drugs are advised to add low-dose slowly up to meet the disease
Risk tolerance of the largest volume.
(C) acridine Dihydroartemisinin HD lack of reductase type: diet control such as "typical phenylketonuria", BH4 and the hub of God
By conduction pioneer supplementary material such as "Des tetrahydro Health neopterin synthesis lack of type", adding folinic acid.
Three, phenylketonuria confirmation and differential diagnosis
PKU neonatal screening is to provide the best method for early diagnosis. The most effective screening methods are measured filter
Paper blood spot samples of amphetamine acid, when the concentration is higher than 2mg/dL blood should be further reviewed. Phenylpropanoid
Acid concentrations continued to rise if the phenomenon, that is, there should be recognition and differential diagnosis. This screening during the neonatal period
Type of amino acid metabolic disorder diseases, it should be noted whether the cases have sufficient intake of protein (breast-feeding 48
Hours or more), in order to avoid the emergence of false-negative.
PKU identified projects should include:
(1) receive specialist training there is a pediatrician clinical evaluation.
(B) Analysis of blood amino acids.
(C) of the urine organic acids by gas chromatography mass spectrometry (GC / Mass)
(D) in urine by high performance liquid chromatography (HPLC) quantitative neopterin (neopterin; N) and biopterin (biopterin;
B) the content, and calculate the percentage of Health neopterin ratio B% = [B / (B + N)] × 100%.
(V) erythrocyte DHPR activity quantitatively.
(Vi) BH4 oral loading test (BH4 loading test): the blood concentration of phenylalanine in the oral BH4
(7.5 mg / kg) 4-6 hours later, down to the following 2mg/dl that the case has taken on the reaction of BH4
(responsive); if no reduced phenylalanine phenomenon, namely, that cases of BH4 without the use of anti -
Should be (nonresponsive).
The differential diagnosis of PKU
Through the above assessment and testing, if blood phenylalanine increased, but normal or low tyrosine and
Ketones in urine has phenylpropanoid metabolite abnormalities can be inferred by reason of PKU patients. And further identification of
Case for what type of phenylketonuria. Methods of identification are as follows:
(A) typical PKU: B% of normal (or high), BH4 oral loading test without reaction, DHPR activity is
Regular.
(B) GTPCHI lack of type PKU: B% normal, but the content of N and B is very low, BH4 oral loading
Test reaction has, DHPR activity normal.
(C) PTPS or SR-type lack of PKU: B% <5%, BH4 oral loading test has reaction, DHPR live
Of normal.
(Iv) DHPR lack of type PKU: B%> 80%, BH4 oral loading test partial response, DHPR live
Is very low.
(E) PCD type lack of PKU: high-performance liquid chromatography in the urine, there are a large number of 7 - biopterin
(7-biopterin) material.
Wednesday, March 11, 2009
Phenylketonuria
First, the preamble:
1, disease name:
PKU (Phenylketonuria), referred to as PKU.
2, Origin:
Dr.Folling Norway in 1934 at familial mental retardation found in the urine of patients with special triteness Taste
, Was later learned the substances are phenylketonuria (phenylpyruvic acid), which has sugar and urine sugar
Urine disease is nothing to do officially named in 1937 for phenylketonuria (phenylketonuria; PKU).
Second, epidemiological studies:
Incidence:
Phenylketonuria is currently the most common congenital genetic metabolic diseases, PKU incidence in Europe and America
For the ten thousandth, 1/30000 about our country's statistics. Europe and the United States the vast majority of PKU patients for
Food-type patients, and patients with drug-based incidence is extremely rare, Taiwan District, one of phenylketonuria due to BH4
Caused by the lack of phenylketonuria is as high as 33% ~ 45%.
Three, pathogenesis:
Heterotypic phenylketonuria (BH4 deficiency) is an autosomal recessive genetic disease of amino acid metabolic disorders
Disease.
Phenylalanine (phenylalanine) amino acids for the human body must be the main metabolic reactions of amphetamine
Acid (PHE) by phenylalanine hydroxylation (PAH), BH4 Des substances such as the role of hydroxylation of tyrosine into
(Tyrosine). Heterotypic phenylketonuria because PAH hydroxylation are required for BH4 Des
(Tetrahydrobiopterin) plane of the metabolic process happen impaired, unable to generate sufficient BH4 supply PAH
Use, resulting in phenylalanine can not be successfully converted into tyrosine, and the substantial accumulation in the body, thereby producing
Health lot of toxic metabolites. Under normal circumstances, BH4 from GTP are a series of anti -
Should be, including the GTP-Cyclohydrolase and 6-Pyruvoyltetrahydropterin Synthase (6PTS)
Such as the role of enzyme synthesis. Involved in hydroxylation of phenylalanine after hydrolysis by
Dihydropteridine Reductase DHPR restore BH4 form a network for the application cycle. BH4
Not only involved in hydroxylation of phenylalanine into tyrosine, are also involved in hydroxylation of tyrosine into DOPA and tryptophan
2
(Tryptophan) hydroxylation into 5-OH Tryptophan response. One of DOPA and 5-OH
Tryptophan conductive material for the central nervous system Dopamine and serotonin pioneer material. So
If the lack of BH4 Des , then the three reactions are blocked, this time not only of high phenylalanine disease
Symptoms, but also because of the lack of central nervous conduction material, and the emergence of many neurological symptoms.
Currently known to have the following five different enzymes will cause a lack of metabolism phenylketonuria Machine impaired:
● phenylalanine hydroxylation enzyme (PAH)
● guanine nucleoside triphosphate cyclohydrolase enzyme hydrolysis (GTPCHI)
● C dione tetrahydro biopterin synthase (PTPS)
● HD-acridine Dihydroartemisinin reductase (DHPR)
● amine methanol dehydration neopterin enzyme (PCD)
Domestic common phenylketonuria has three types are as follows:
1. Phenylalanine hydroxylase (referred to as PAH) lack of phenylketonuria:
Phenylketonuria mostly belong to this type, so called "classic PKU", such a disease
Child is low-phenylalanine diet to treat, so called "diet therapy type phenylketonuria."
2. Tetrahydro neopterin Health (hereinafter referred to BH4) synthesis of a lack of coenzyme type phenylketonuria:
The lack of BH4 synthesis may be known by three different enzymes caused by a lack of domestic this type
Most of the children are 6-PTPS enzyme caused by the lack of the lack of BH4 synthesis. This type of domestic benzene
Ketone urine disease accounts for about 20% of all PKU to 30%. This type untreated phenylketonuria, the often
Severe neurological symptoms (Example: pumping bear), are given to BH4 treatment and nerve conduction to more complex
Quality (Example: L - Dopa, 5 - HTP), such as drugs, so it was commonly known as "drug therapy type benzene ketone
Urine disease. "
3. Dihydroartemisinin neopterin reductase (the DHPR) lack of phenylketonuria:
BH4 metabolism DHPR plays an important role, DHPR makes BH4 recycling not
Scarce. DHPR resulted in the lack of BH4 can not be recycled, resulting in the lack of BH4. Therefore DHPR
Lack of "BH4 synthesis of a lack of coenzyme phenylketonuria type" of a type. Treatment methods are "drink
Fresh control "and" drug "(Example: BH4 and nerve conduction to more material) a two-pronged approach, adding
Flinic acid.
3
Four clinical symptoms:
1, the lack of hydroxylation enzyme alanine (PAH):
Resulted in typical phenylketonuria. Their clinical symptoms showed a yellow hair, pale skin dry and intelligent residual
Impaired sequelae.
2, the lack of guanine nucleoside triphosphate cyclohydrolase enzyme hydrolysis (Gtp cyclohydrolase I; GTPCHI), C
Dione tetrahydro biopterin synthase (6-pyruvoyl tetrahydropterin synthase; PTPS), dihydrotestosterone
HD-acridine reductase (dihydropteridine reductase; DHPR):
The lack of these three enzymes would cause either lack of BH4. Its typical clinical symptoms apart from phenylketonuria
Some of the symptoms, there are serious neurological symptoms (such as convulsions), growth retardation, easy infection.
3, chronic lack of congenital hemolytic anemia:
Although BH4 deficiencies may also result, but the clinical symptoms of mild, may not need treatment. PKU in China
Patients with about 20% ~ 30% for lack of tetrahydro Health neopterin type, with results to differ materially from those in Western countries,
The special needs of differential diagnosis in order to adopt the correct method of treatment.
Friday, diagnosis:
• PKU identified projects should include:
1, receive specialist training, as there is a pediatrician in clinical evaluation.
2, blood amino acid analysis.
3, urine organic acids by gas chromatography mass spectrometry (GC / Mass)
4, urine by high performance liquid chromatography (HPLC) quantitative neopterin (neopterin; N) and biopterin (biopterin;
B) the content, and calculate the percentage of Health neopterin ratio B% = [B / (B + N)] × 100%.
5, erythrocyte DHPR activity quantitatively.
6, BH4 oral loading test (BH4 loading test): the blood concentration of phenylalanine in the oral
BH4 (7.5 mg / kg) 4-6 hours later, down to the following 2mg/dl that case the taking of BH4
There is reaction (responsive); if no reduced phenylalanine phenomenon, namely the express cases of BH4
Taking non-response (nonresponsive).
• PKU differential diagnosis
Through the above assessment and testing, if blood phenylalanine increased, but normal or low tyrosine and urine
Medium has phenylpropanoid metabolite abnormalities ketones can be inferred by reason of PKU patients. And further identification
Cases for what type of phenylketonuria. Methods of identification are as follows:
4
1, the typical PKU: B% of normal (or high), BH4 oral loading test without reaction, DHPR activity
Normal.
2, GTPCHI lack of type PKU: B% normal, but the content of N and B is very low, BH4 oral
Load test response has, DHPR activity normal.
3, PTPS or SR-type lack of PKU: B% <5%, BH4 oral loading test has reaction, DHPR
Normal activity.
4, DHPR type lack of PKU: B%> 80%, BH4 oral loading test partial response, DHPR
Activity is very low.
5, PCD type lack of PKU: high-performance liquid chromatography in the urine, there are a large number of 7 - biopterin
(7-biopterin) material.
6, treatment:
To prevent the occurrence of sequelae of PKU, except to be the right remedy, and the sooner the better therapeutic effect. Root
According to foreign literature, the treatment of patients at one month, the average IQ of 95, one to two months
Patients before treatment, the average IQ of 85; and advanced medical treatment or treatment, the average IQ
For 53-45. According to the experience of domestic and foreign literature, BH4 treatment type lack of a good prognosis, especially
Their neurological symptoms are the control and the growth and development, if that is during the neonatal period for treatment, their IQ can be
Achieve the normal standard.
PKU patients with various types of treatment are as follows:
1, the typical PKU: given the low phenylalanine diet control, so that the blood phenylalanine concentration remained at
4-8mg/dl, but we must also consider the protein, calories, such as balanced nutrition to maintain the patient's normal growth.
The longer the better diet control, at least to maintain the six-year-old. Female cases of child-bearing age should be continued until after
In order to avoid future occurrence of maternal phenylketonuria (maternal PKU), congenital disabilities caused by the next generation of middle class children
Health.
2, Des tetrahydro Health Synthesis neopterin lack of type (guanine nucleoside triphosphate cyclohydrolase enzyme hydrolysis, C HD-tetrahydro dione
Methotrexate synthetic enzyme): given BH4 (1-5 mg / kg / day), so that the blood phenylalanine concentration of at least maintained at
4mg/dL following. Because patients have neurological symptoms, have to add a pioneer in the central nervous conduction material,
L-dopa (5-15 mg / kg / day) and 5-hydroxy tryptophan (4-10 mg / kg / day),
carbidopa (1-2mg/kg/day), nerve conduction drugs are advised to add low-dose slowly up to meet the patients
Maximum tolerated volume.
5
3, Dihydroartemisinin lack of HD-acridine reductase type: diet control such as "typical phenylketonuria", BH4, and the central nervous
Conduction pioneer supplementary material such as "Des tetrahydro Health neopterin synthesis lack of type", adding folinic acid.
Seven, prevention and screening:
At present, BH4 Des gene sequencing has been out of the use of molecular biology (gene mutation analysis) of
Ways, for one child up for phenylketonuria heterotypic parents and patients, its detection of defective genes,
To identify and confirm point mutations, and then in antenatal mothers (after 16 weeks of pregnancy) for amniocentesis samples
Fetal amniotic fluid cells for the detection of DNA analysis, would be effective for prenatal diagnosis, was informed that the fetus
Whether the patients.
PKU neonatal screening is to provide the best method for early diagnosis. The most effective screening methods are measured filter
Paper blood spot samples of amphetamine acid, when the concentration is higher than 2mg/dL blood should be further rehabilitation
Search. Phenylalanine concentrations continue to rise if the phenomenon, that is, there should be recognition and differential diagnosis. In the new
Period of screening babies amino acid metabolic disorders such diseases, it should be noted whether the cases had a sufficient intake
Enough protein (breast-feeding for more than 48 hours), in order to avoid the emergence of false-negative.
1, disease name:
PKU (Phenylketonuria), referred to as PKU.
2, Origin:
Dr.Folling Norway in 1934 at familial mental retardation found in the urine of patients with special triteness Taste
, Was later learned the substances are phenylketonuria (phenylpyruvic acid), which has sugar and urine sugar
Urine disease is nothing to do officially named in 1937 for phenylketonuria (phenylketonuria; PKU).
Second, epidemiological studies:
Incidence:
Phenylketonuria is currently the most common congenital genetic metabolic diseases, PKU incidence in Europe and America
For the ten thousandth, 1/30000 about our country's statistics. Europe and the United States the vast majority of PKU patients for
Food-type patients, and patients with drug-based incidence is extremely rare, Taiwan District, one of phenylketonuria due to BH4
Caused by the lack of phenylketonuria is as high as 33% ~ 45%.
Three, pathogenesis:
Heterotypic phenylketonuria (BH4 deficiency) is an autosomal recessive genetic disease of amino acid metabolic disorders
Disease.
Phenylalanine (phenylalanine) amino acids for the human body must be the main metabolic reactions of amphetamine
Acid (PHE) by phenylalanine hydroxylation (PAH), BH4 Des substances such as the role of hydroxylation of tyrosine into
(Tyrosine). Heterotypic phenylketonuria because PAH hydroxylation are required for BH4 Des
(Tetrahydrobiopterin) plane of the metabolic process happen impaired, unable to generate sufficient BH4 supply PAH
Use, resulting in phenylalanine can not be successfully converted into tyrosine, and the substantial accumulation in the body, thereby producing
Health lot of toxic metabolites. Under normal circumstances, BH4 from GTP are a series of anti -
Should be, including the GTP-Cyclohydrolase and 6-Pyruvoyltetrahydropterin Synthase (6PTS)
Such as the role of enzyme synthesis. Involved in hydroxylation of phenylalanine after hydrolysis by
Dihydropteridine Reductase DHPR restore BH4 form a network for the application cycle. BH4
Not only involved in hydroxylation of phenylalanine into tyrosine, are also involved in hydroxylation of tyrosine into DOPA and tryptophan
2
(Tryptophan) hydroxylation into 5-OH Tryptophan response. One of DOPA and 5-OH
Tryptophan conductive material for the central nervous system Dopamine and serotonin pioneer material. So
If the lack of BH4 Des , then the three reactions are blocked, this time not only of high phenylalanine disease
Symptoms, but also because of the lack of central nervous conduction material, and the emergence of many neurological symptoms.
Currently known to have the following five different enzymes will cause a lack of metabolism phenylketonuria Machine impaired:
● phenylalanine hydroxylation enzyme (PAH)
● guanine nucleoside triphosphate cyclohydrolase enzyme hydrolysis (GTPCHI)
● C dione tetrahydro biopterin synthase (PTPS)
● HD-acridine Dihydroartemisinin reductase (DHPR)
● amine methanol dehydration neopterin enzyme (PCD)
Domestic common phenylketonuria has three types are as follows:
1. Phenylalanine hydroxylase (referred to as PAH) lack of phenylketonuria:
Phenylketonuria mostly belong to this type, so called "classic PKU", such a disease
Child is low-phenylalanine diet to treat, so called "diet therapy type phenylketonuria."
2. Tetrahydro neopterin Health (hereinafter referred to BH4) synthesis of a lack of coenzyme type phenylketonuria:
The lack of BH4 synthesis may be known by three different enzymes caused by a lack of domestic this type
Most of the children are 6-PTPS enzyme caused by the lack of the lack of BH4 synthesis. This type of domestic benzene
Ketone urine disease accounts for about 20% of all PKU to 30%. This type untreated phenylketonuria, the often
Severe neurological symptoms (Example: pumping bear), are given to BH4 treatment and nerve conduction to more complex
Quality (Example: L - Dopa, 5 - HTP), such as drugs, so it was commonly known as "drug therapy type benzene ketone
Urine disease. "
3. Dihydroartemisinin neopterin reductase (the DHPR) lack of phenylketonuria:
BH4 metabolism DHPR plays an important role, DHPR makes BH4 recycling not
Scarce. DHPR resulted in the lack of BH4 can not be recycled, resulting in the lack of BH4. Therefore DHPR
Lack of "BH4 synthesis of a lack of coenzyme phenylketonuria type" of a type. Treatment methods are "drink
Fresh control "and" drug "(Example: BH4 and nerve conduction to more material) a two-pronged approach, adding
Flinic acid.
3
Four clinical symptoms:
1, the lack of hydroxylation enzyme alanine (PAH):
Resulted in typical phenylketonuria. Their clinical symptoms showed a yellow hair, pale skin dry and intelligent residual
Impaired sequelae.
2, the lack of guanine nucleoside triphosphate cyclohydrolase enzyme hydrolysis (Gtp cyclohydrolase I; GTPCHI), C
Dione tetrahydro biopterin synthase (6-pyruvoyl tetrahydropterin synthase; PTPS), dihydrotestosterone
HD-acridine reductase (dihydropteridine reductase; DHPR):
The lack of these three enzymes would cause either lack of BH4. Its typical clinical symptoms apart from phenylketonuria
Some of the symptoms, there are serious neurological symptoms (such as convulsions), growth retardation, easy infection.
3, chronic lack of congenital hemolytic anemia:
Although BH4 deficiencies may also result, but the clinical symptoms of mild, may not need treatment. PKU in China
Patients with about 20% ~ 30% for lack of tetrahydro Health neopterin type, with results to differ materially from those in Western countries,
The special needs of differential diagnosis in order to adopt the correct method of treatment.
Friday, diagnosis:
• PKU identified projects should include:
1, receive specialist training, as there is a pediatrician in clinical evaluation.
2, blood amino acid analysis.
3, urine organic acids by gas chromatography mass spectrometry (GC / Mass)
4, urine by high performance liquid chromatography (HPLC) quantitative neopterin (neopterin; N) and biopterin (biopterin;
B) the content, and calculate the percentage of Health neopterin ratio B% = [B / (B + N)] × 100%.
5, erythrocyte DHPR activity quantitatively.
6, BH4 oral loading test (BH4 loading test): the blood concentration of phenylalanine in the oral
BH4 (7.5 mg / kg) 4-6 hours later, down to the following 2mg/dl that case the taking of BH4
There is reaction (responsive); if no reduced phenylalanine phenomenon, namely the express cases of BH4
Taking non-response (nonresponsive).
• PKU differential diagnosis
Through the above assessment and testing, if blood phenylalanine increased, but normal or low tyrosine and urine
Medium has phenylpropanoid metabolite abnormalities ketones can be inferred by reason of PKU patients. And further identification
Cases for what type of phenylketonuria. Methods of identification are as follows:
4
1, the typical PKU: B% of normal (or high), BH4 oral loading test without reaction, DHPR activity
Normal.
2, GTPCHI lack of type PKU: B% normal, but the content of N and B is very low, BH4 oral
Load test response has, DHPR activity normal.
3, PTPS or SR-type lack of PKU: B% <5%, BH4 oral loading test has reaction, DHPR
Normal activity.
4, DHPR type lack of PKU: B%> 80%, BH4 oral loading test partial response, DHPR
Activity is very low.
5, PCD type lack of PKU: high-performance liquid chromatography in the urine, there are a large number of 7 - biopterin
(7-biopterin) material.
6, treatment:
To prevent the occurrence of sequelae of PKU, except to be the right remedy, and the sooner the better therapeutic effect. Root
According to foreign literature, the treatment of patients at one month, the average IQ of 95, one to two months
Patients before treatment, the average IQ of 85; and advanced medical treatment or treatment, the average IQ
For 53-45. According to the experience of domestic and foreign literature, BH4 treatment type lack of a good prognosis, especially
Their neurological symptoms are the control and the growth and development, if that is during the neonatal period for treatment, their IQ can be
Achieve the normal standard.
PKU patients with various types of treatment are as follows:
1, the typical PKU: given the low phenylalanine diet control, so that the blood phenylalanine concentration remained at
4-8mg/dl, but we must also consider the protein, calories, such as balanced nutrition to maintain the patient's normal growth.
The longer the better diet control, at least to maintain the six-year-old. Female cases of child-bearing age should be continued until after
In order to avoid future occurrence of maternal phenylketonuria (maternal PKU), congenital disabilities caused by the next generation of middle class children
Health.
2, Des tetrahydro Health Synthesis neopterin lack of type (guanine nucleoside triphosphate cyclohydrolase enzyme hydrolysis, C HD-tetrahydro dione
Methotrexate synthetic enzyme): given BH4 (1-5 mg / kg / day), so that the blood phenylalanine concentration of at least maintained at
4mg/dL following. Because patients have neurological symptoms, have to add a pioneer in the central nervous conduction material,
L-dopa (5-15 mg / kg / day) and 5-hydroxy tryptophan (4-10 mg / kg / day),
carbidopa (1-2mg/kg/day), nerve conduction drugs are advised to add low-dose slowly up to meet the patients
Maximum tolerated volume.
5
3, Dihydroartemisinin lack of HD-acridine reductase type: diet control such as "typical phenylketonuria", BH4, and the central nervous
Conduction pioneer supplementary material such as "Des tetrahydro Health neopterin synthesis lack of type", adding folinic acid.
Seven, prevention and screening:
At present, BH4 Des gene sequencing has been out of the use of molecular biology (gene mutation analysis) of
Ways, for one child up for phenylketonuria heterotypic parents and patients, its detection of defective genes,
To identify and confirm point mutations, and then in antenatal mothers (after 16 weeks of pregnancy) for amniocentesis samples
Fetal amniotic fluid cells for the detection of DNA analysis, would be effective for prenatal diagnosis, was informed that the fetus
Whether the patients.
PKU neonatal screening is to provide the best method for early diagnosis. The most effective screening methods are measured filter
Paper blood spot samples of amphetamine acid, when the concentration is higher than 2mg/dL blood should be further rehabilitation
Search. Phenylalanine concentrations continue to rise if the phenomenon, that is, there should be recognition and differential diagnosis. In the new
Period of screening babies amino acid metabolic disorders such diseases, it should be noted whether the cases had a sufficient intake
Enough protein (breast-feeding for more than 48 hours), in order to avoid the emergence of false-negative.
Phenylketonuria
What is phenylketonuria:
Phenylketonuria is one of the first in 1934 by Dr. Folling at a pair of brothers have been found mentally retarded, because urine contains many benzene acid, named because of phenylketonuria, which has sugar in urine are unrelated to diabetes. The main causes of the disease in the human body will be necessary for the phenylalanine amino acid (phenylalanine) into tyrosine metabolism (typrosine) occurred in the path of the metabolic defects, which led to substantial accumulation of phenylalanine in the body, and then after metabolism by the human body a lot of acid and amphetamine-related metabolite, resulting in brain injury patients.
Such as early treatment of patients will not have a serious mental retardation, because the disease of the brain injuries are caused by progressive in nature, so many asymptomatic newborn infant, at about 3 ~ 4 months or so before the symptoms appear slowly . The symptoms of vomiting, skin and hair color , eczema, growth retardation, urine and body odor Khan has mycophenolate draw bear, tremor and abnormal movements. If only start treatment, the brain nerve has caused irreparable harm to the.
Correct early diagnosis
How the disease before the correct diagnosis and proper treatment are the treatment of phenylketonuria of the most important job. Newborn screening and thus to achieve this goal is the best way. In 73 years in our country begin the implementation of neonatal screening, before that many experts believe that Taiwan has no such patients, screening does not seem necessary, however, facts have proven that indeed the people of the existence of genetic diseases (about 1/30000 ), Prior to this, many patients were misdiagnosed as cerebral palsy, mental retardation has been housed in institutions, failed to receive proper treatment, a great pity.
Why phenylketonuria
Phenylketonuria is a recessive genetic disease, parents of patients with a mutation in the gene, but no clinical symptoms known as carriers. Patients themselves must be at the same time with two mutant genes (by the parents each have a mutated gene) will be the incidence; except close relatives pass extra-marital affairs, there are generally encountered by parents with a mutation probability is not high, so parents often said: "We both have family in the absence of such sick ah! how could give a child this genetic?" But as long as both parents are carriers, then the next viviparous a phenylketonuria (PKU) patients of probability as high as 1 / 4.
Phenylketonuria treatment programs
Regarding the treatment of this disease can be divided into two categories: First, food type, are another type of drug. Food type of illness, was made to cater for sick liver phenylalanine hydride (referred to as PAH) caused by their own shortcomings, its treatment for diet control, that is, foods containing phenylalanine excess food, do not eat, but at nature almost protein-containing food, phenylalanine are high, such as: eggs, meat, fish, beans and so on, both containing amphetamine acid is very high, so neither can eat these things. Even rice, flour and other basic foods, also contain considerable phenylalanine, their intake of these children will also have restrictions, so the inconvenience and pain of life is often not an ordinary person can understand, in order to complement the other body essential amino acids required patients must eat a special phenylalanine-free powdered milk, in order to maintain the body's growth and operation of the high price of such milk powder, non-average family can afford.
As for drug-type patients, which is due to PHA Des BH4 metabolism path is a problem, they can not produce sufficient quantities of BH4 for use PAH. Such patients can be added to the treatment of BH4, but BH4 is also a brain neurotransmitter other path of Des important, because BH4 itself can not be brain barrier and can not reach the brain for the brain to use, so such children from urine side effects to add some great nerve conduction material, such as DOPA (DOPA), 5HTP and so on.
On such patients in clinical'd like to achieve the best control, there are still many questions need to be resolved. Control of this disease has now reached a consensus, which is "life-long control." Early years, there have been many doctors believe that the child control to 6-year-old will be able to relax after the treatment, but later confirmed that these are no longer strictly control the children, often also happen disorders emotional instability and physical and psychological symptoms.
Note the daily life of
For example, when a patient's resistance to the period when young people are often the lot of children do not want to own different peers, while giving up diet therapy and his companions to eat the same food, causing a lot of acts on the deviation, more Some patients at this time, unfortunately, if the pregnancy will have a very serious abuse of the deformity, this is our genetic metabolic physician Branch do not want to see things very much, we do not want to be hard to come back to save the children, again by injury, or to allow society to pay a higher price. So how do we help these children, know them, give them timely encouragement and support to enable them to tide over the difficulties of Enron, which we are looking forward to the Center; because these patients to eat food are extremely limited, and the special milk special taste, it is hard to swallow.
However, this disease has already developed a lot of low-phenylalanine foods for PKU patients to use, but do not even have a domestic manufacturer is willing to import these products, because too few patients and low profits, not to mention the overwhelming majority of The home also can not afford the cost of these special food, in the absence of some food to eat, it is hoped that these patients can have a good control of their diet, it is a bit imposing.
Phenylketonuria is one of the first in 1934 by Dr. Folling at a pair of brothers have been found mentally retarded, because urine contains many benzene acid, named because of phenylketonuria, which has sugar in urine are unrelated to diabetes. The main causes of the disease in the human body will be necessary for the phenylalanine amino acid (phenylalanine) into tyrosine metabolism (typrosine) occurred in the path of the metabolic defects, which led to substantial accumulation of phenylalanine in the body, and then after metabolism by the human body a lot of acid and amphetamine-related metabolite, resulting in brain injury patients.
Such as early treatment of patients will not have a serious mental retardation, because the disease of the brain injuries are caused by progressive in nature, so many asymptomatic newborn infant, at about 3 ~ 4 months or so before the symptoms appear slowly . The symptoms of vomiting, skin and hair color , eczema, growth retardation, urine and body odor Khan has mycophenolate draw bear, tremor and abnormal movements. If only start treatment, the brain nerve has caused irreparable harm to the.
Correct early diagnosis
How the disease before the correct diagnosis and proper treatment are the treatment of phenylketonuria of the most important job. Newborn screening and thus to achieve this goal is the best way. In 73 years in our country begin the implementation of neonatal screening, before that many experts believe that Taiwan has no such patients, screening does not seem necessary, however, facts have proven that indeed the people of the existence of genetic diseases (about 1/30000 ), Prior to this, many patients were misdiagnosed as cerebral palsy, mental retardation has been housed in institutions, failed to receive proper treatment, a great pity.
Why phenylketonuria
Phenylketonuria is a recessive genetic disease, parents of patients with a mutation in the gene, but no clinical symptoms known as carriers. Patients themselves must be at the same time with two mutant genes (by the parents each have a mutated gene) will be the incidence; except close relatives pass extra-marital affairs, there are generally encountered by parents with a mutation probability is not high, so parents often said: "We both have family in the absence of such sick ah! how could give a child this genetic?" But as long as both parents are carriers, then the next viviparous a phenylketonuria (PKU) patients of probability as high as 1 / 4.
Phenylketonuria treatment programs
Regarding the treatment of this disease can be divided into two categories: First, food type, are another type of drug. Food type of illness, was made to cater for sick liver phenylalanine hydride (referred to as PAH) caused by their own shortcomings, its treatment for diet control, that is, foods containing phenylalanine excess food, do not eat, but at nature almost protein-containing food, phenylalanine are high, such as: eggs, meat, fish, beans and so on, both containing amphetamine acid is very high, so neither can eat these things. Even rice, flour and other basic foods, also contain considerable phenylalanine, their intake of these children will also have restrictions, so the inconvenience and pain of life is often not an ordinary person can understand, in order to complement the other body essential amino acids required patients must eat a special phenylalanine-free powdered milk, in order to maintain the body's growth and operation of the high price of such milk powder, non-average family can afford.
As for drug-type patients, which is due to PHA Des BH4 metabolism path is a problem, they can not produce sufficient quantities of BH4 for use PAH. Such patients can be added to the treatment of BH4, but BH4 is also a brain neurotransmitter other path of Des important, because BH4 itself can not be brain barrier and can not reach the brain for the brain to use, so such children from urine side effects to add some great nerve conduction material, such as DOPA (DOPA), 5HTP and so on.
On such patients in clinical'd like to achieve the best control, there are still many questions need to be resolved. Control of this disease has now reached a consensus, which is "life-long control." Early years, there have been many doctors believe that the child control to 6-year-old will be able to relax after the treatment, but later confirmed that these are no longer strictly control the children, often also happen disorders emotional instability and physical and psychological symptoms.
Note the daily life of
For example, when a patient's resistance to the period when young people are often the lot of children do not want to own different peers, while giving up diet therapy and his companions to eat the same food, causing a lot of acts on the deviation, more Some patients at this time, unfortunately, if the pregnancy will have a very serious abuse of the deformity, this is our genetic metabolic physician Branch do not want to see things very much, we do not want to be hard to come back to save the children, again by injury, or to allow society to pay a higher price. So how do we help these children, know them, give them timely encouragement and support to enable them to tide over the difficulties of Enron, which we are looking forward to the Center; because these patients to eat food are extremely limited, and the special milk special taste, it is hard to swallow.
However, this disease has already developed a lot of low-phenylalanine foods for PKU patients to use, but do not even have a domestic manufacturer is willing to import these products, because too few patients and low profits, not to mention the overwhelming majority of The home also can not afford the cost of these special food, in the absence of some food to eat, it is hoped that these patients can have a good control of their diet, it is a bit imposing.
Phenylketonuria (Tetrahydrobiopterin deficiency)
Biochemical principles of:
Phenylalanine (phenylalanine) amino acids for the human body must be the main metabolic reactions of phenylalanine (PHE) by oxygen, phenylalanine hydroxylation (PAH), BH4 Des , and other substances into the role of tyrosine hydroxylation (Tyrosine). Heterotypic phenylketonuria because PAH hydroxylation are required for BH4 Des (Tetrahydrobiopterin) plane of the metabolic process happen impaired, unable to generate sufficient supply of PAH using BH4, resulting in phenylalanine can not be smoothly converted into tyrosine, and in vivo with substantial accumulation, which lead to many toxic metabolites, can cause serious long-term intelligence on obstacles.
Under normal circumstances, BH4 from GTP are a series of reactions, including the GTP-Cyclohydrolase and 6-Pyruvoyltetrahydropterin Synthase (6PTS), such as the role of enzyme synthesis. Involved in hydroxylation of phenylalanine after hydrolysis by Dihydropteridine Reductase DHPR back to BH4 cycle of the application to form a network. BH4 not only involved in hydroxylation of phenylalanine into tyrosine, are also involved in hydroxylation of tyrosine into DOPA and Tryptophan (Tryptophan) hydroxylation into 5-OH Tryptophan response. One of DOPA and 5-OH Tryptophan conductive material for the central nervous system Dopamine and serotonin pioneer material. So if the lack of BH4 Des , then the three reactions are blocked, there will be high at this time not only the symptoms of phenylalanine, but also because of the lack of central nervous conduction material, and the emergence of many neurological symptoms.
Genetic mechanisms and prenatal diagnosis:
Heterotypic phenylketonuria (BH4 deficiency) is an autosomal recessive genetic disorders of amino acid metabolism, both parents are carriers of the recessive (the Parent with a defective gene, but no clinical symptoms ), the patient must at the same time with two defective genes (by the parents each have a) only the incidence, so as long as both parents are carriers, then the next pair subtidal fetal chance for phenylketonuria patients are up to a quarter of patients with no chance of suffering from gender-neutral.
At present, BH4 Des gene sequencing has been out of the use of molecular biology (gene mutation analysis) method, for one child up for phenylketonuria heterotypic parents and patients, its detection of defective genes, to identify and confirmed gene mutation point, and then in antenatal mothers (after 16 weeks of pregnancy) for amniocentesis samples of amniotic fluid fetal cells for DNA detection analysis, would be effective for prenatal diagnosis, for patients to know whether the fetus.
Incidence:
According to literature reports, the average incidence of PKU is about one ten thousandth, but there is a lot of regional and racial differences, which were caused by the lack of BH4 phenylketonuria only 1 ~ 3%. At present, the Taiwan region is about the incidence of phenylketonuria 1/40000, which were caused by the lack of BH4 phenylketonuria is as high as 33% ~ 45%, with the western countries results to differ materially.
Confirm the diagnosis:
(A) set up a correct early diagnosis: Neonatal Screening
Clinically, the baby was born because many asymptomatic at birth of about three, four months later, the accumulation of excessive blood product of phenylalanine metabolism of toxic symptoms only slowly, has often resulted in irreversible damage. Therefore, prior to the onset of how to obtain the correct diagnosis and appropriate treatment, neonatal screening for early detection are the best way. At birth 48 hours over 24 hours after feeding, from the heel to take a small amount of blood, determination of the rate of bleeding in the amphetamine-chip samples of the acid content, when the concentration is higher than 2mg/dLblood should be further reviewed, and the concentration of phenylalanine if the phenomenon continued to rise, (higher than 4mg/dLblood) that should be carried out to confirm the diagnosis.
(B) confirmation and differential diagnosis of the Project:
1. Accepted by the specialist training there is the clinical assessment of a pediatrician.
2. Laboratory confirmation for the sub-Ways:
(1) Does the blood amino acid analysis of blood to detect blood phenylalanine and tyrosine concentrations
(2) urine analysis of organic acids by gas chromatography mass spectrometry (GC / Mass)
(3) high performance liquid chromatography quantitative urine neopterin (Neopterin) and biopterin (Biopterin), and calculate the% B = B / N + BX 100%
(4) quantitative determination of erythrocyte DHPR activity
(5) When the blood PHE> 10mg/dl, can carry out the Des BH4 loading test (BH4 loading test). Fasting given BH4 7.5mg/kg ~ 20mg/kg, 30 minutes after feeding, at 2hr, 4hr, 8hr, 24hr, 48hr were measured in blood phenylalanine concentration and proportion of urine analysis Pterins, if the value at BH4 taking PHE 4-6 hours after the resumption of normal PHE <2mg/dl, for BH4 has reactive, if not lower, compared with BH4 not reactive.
(6) BH4 deficiency Des classification:
a, if the% B of normal, and Neopterin and Biopterin content were very low, BH4 Des have the load test for the reaction, they belong to the lack of GTP-cyclohydrolase type.
b, if the% B <5, the Neopterin and high content of, BH4 Des have the load test for responders, it may belong to the absence of 6-PTS-type.
C, if the% B> 80, or normal, and high-Biopterin content, BH4 Des the load test for the partial or no response, they belong to the absence of DHPR Restore type, determination of enzyme can be used to determine the red blood cells.
Clinical symptoms:
If the substantial accumulation of phenylalanine in the body, metabolism in the human body have a lot of amphetamine after acid-related metabolites, can cause the patient's brain injury, early treatment will not have a serious mental retardation. Since the disease of the brain caused by injury are progressive in nature, so many babies born asymptomatic, at about 3-4 months after the symptoms occur only slowly. The symptoms of vomiting, skin and hair color , eczema, growth retardation, urine and body odor Khan has mycophenolate draw bear, tremor and abnormal movements. If the wait time before beginning treatment, often the brain nerve has resulted in irreparable damage to the.
Against the lack of BH4 Des type of patients, apart from the above-mentioned symptoms, but also because of the lack of BH4 to merge the central nervous system conduction material and the lack of Dopamine and serotonin, and the conduct of serious central nervous system symptoms such as muscle tension reduction, beyond the control of convulsions , severe growth retardation, infection symptoms such as easy.
Treatment and prognosis:
(1) For the lack of BH4-type patients, the restriction of dietary phenylalanine method of treatment, and can not effectively prevent the central nervous system symptoms. Single use in patients with BH4 treatment can control blood phenylalanine concentration, but not easy BH4 itself through the brain barrier and can not reach the brain for brain conduction, so that caused the lack of Dopamine and serotonin can cause intellectual and spiritual obstacles Therefore, in patients with phenylketonuria need to be complemented by special-shaped above-mentioned neurotransmitter precursors for treatment, such as: dopa (L-Dopa), HTP (5-hydroxytryptophan), etc.
(B) The principle of treatment
1, BH4 (10mg BH4 2HCl, 50mg ascorbic acid, 25mg N-acetyl-L-cysteine):
Oral BH4 (10mg/tab) to 1-5mg/kg/day dose of treatment, so that the concentration of blood phenylalanine control in the long term <2mg/dl. Medication should be an empty stomach 30 minutes before eating, not the child could be crushed after the drug dissolved in cold water mixing within 30 minutes of taking finished because of BH4 on the temperature-sensitive, is strictly prohibited when taking a hot brew Moreover due to BH4 easily and with oxygen absorption effect, it should be stored in frozen state (-20. c), the BH4 in unopened -20. Under C can be stored for more than two years, placed in sealed BH4 months at room temperature, the color will become Lunatia, but still more than 99% of the activity, but when BH4 into a dark yellow color when it no longer edible.
2,5-OH tryptophan (5-OHTP: 100mg/Oxitriptan):
After meals, oral 5-OHTP to 4-10mg/kg/day dose of treatment, to add low-dose slowly up the volume, the largest not more than the use of 10mg/kg/day, in order to avoid excessive blood pressure may be a momentary instability, gastrointestinal discomfort, such as nausea, vomiting or diarrhea and other side effects. Has the above-mentioned symptoms need arises to reduce or disable the serious symptoms when treated with steroids can be used. And shall as soon as possible contact with the specialist physician.
3, Sinemet (250mg Levodopa, 50mg Carbidopa / tab):
After meals, oral Sinemet to L-dopa 5-15mg/kg/day, Carbidopa 1-2mg/kg/day dose of treatment to low-dose slowly add up the amount of time, therefore the role of medicine quickly, so dose adjustment period should be to observe the patient's response to the efficacy and side effects, if we find that patients have cramps, trembling, restlessness of the phenomenon, it may be excessive doses, or add the results of drug too fast, if the patient has weakness, or muscle stiffness and other symptoms may arise for the amount of drugs is not enough when there is the above symptoms should contact a doctor as soon as possible with the specialist.
(C) set up the ideal blood PHE control objectives
1, BH4 synthesis lack of type (GTP cylohydrolase and 6-PTS): phe <2mg/dl
2, DHPR restore lack type: phe at 2-6mg/dl between the growth period: phe at between 2-4mg/dl
Phenylalanine (phenylalanine) amino acids for the human body must be the main metabolic reactions of phenylalanine (PHE) by oxygen, phenylalanine hydroxylation (PAH), BH4 Des , and other substances into the role of tyrosine hydroxylation (Tyrosine). Heterotypic phenylketonuria because PAH hydroxylation are required for BH4 Des (Tetrahydrobiopterin) plane of the metabolic process happen impaired, unable to generate sufficient supply of PAH using BH4, resulting in phenylalanine can not be smoothly converted into tyrosine, and in vivo with substantial accumulation, which lead to many toxic metabolites, can cause serious long-term intelligence on obstacles.
Under normal circumstances, BH4 from GTP are a series of reactions, including the GTP-Cyclohydrolase and 6-Pyruvoyltetrahydropterin Synthase (6PTS), such as the role of enzyme synthesis. Involved in hydroxylation of phenylalanine after hydrolysis by Dihydropteridine Reductase DHPR back to BH4 cycle of the application to form a network. BH4 not only involved in hydroxylation of phenylalanine into tyrosine, are also involved in hydroxylation of tyrosine into DOPA and Tryptophan (Tryptophan) hydroxylation into 5-OH Tryptophan response. One of DOPA and 5-OH Tryptophan conductive material for the central nervous system Dopamine and serotonin pioneer material. So if the lack of BH4 Des , then the three reactions are blocked, there will be high at this time not only the symptoms of phenylalanine, but also because of the lack of central nervous conduction material, and the emergence of many neurological symptoms.
Genetic mechanisms and prenatal diagnosis:
Heterotypic phenylketonuria (BH4 deficiency) is an autosomal recessive genetic disorders of amino acid metabolism, both parents are carriers of the recessive (the Parent with a defective gene, but no clinical symptoms ), the patient must at the same time with two defective genes (by the parents each have a) only the incidence, so as long as both parents are carriers, then the next pair subtidal fetal chance for phenylketonuria patients are up to a quarter of patients with no chance of suffering from gender-neutral.
At present, BH4 Des gene sequencing has been out of the use of molecular biology (gene mutation analysis) method, for one child up for phenylketonuria heterotypic parents and patients, its detection of defective genes, to identify and confirmed gene mutation point, and then in antenatal mothers (after 16 weeks of pregnancy) for amniocentesis samples of amniotic fluid fetal cells for DNA detection analysis, would be effective for prenatal diagnosis, for patients to know whether the fetus.
Incidence:
According to literature reports, the average incidence of PKU is about one ten thousandth, but there is a lot of regional and racial differences, which were caused by the lack of BH4 phenylketonuria only 1 ~ 3%. At present, the Taiwan region is about the incidence of phenylketonuria 1/40000, which were caused by the lack of BH4 phenylketonuria is as high as 33% ~ 45%, with the western countries results to differ materially.
Confirm the diagnosis:
(A) set up a correct early diagnosis: Neonatal Screening
Clinically, the baby was born because many asymptomatic at birth of about three, four months later, the accumulation of excessive blood product of phenylalanine metabolism of toxic symptoms only slowly, has often resulted in irreversible damage. Therefore, prior to the onset of how to obtain the correct diagnosis and appropriate treatment, neonatal screening for early detection are the best way. At birth 48 hours over 24 hours after feeding, from the heel to take a small amount of blood, determination of the rate of bleeding in the amphetamine-chip samples of the acid content, when the concentration is higher than 2mg/dLblood should be further reviewed, and the concentration of phenylalanine if the phenomenon continued to rise, (higher than 4mg/dLblood) that should be carried out to confirm the diagnosis.
(B) confirmation and differential diagnosis of the Project:
1. Accepted by the specialist training there is the clinical assessment of a pediatrician.
2. Laboratory confirmation for the sub-Ways:
(1) Does the blood amino acid analysis of blood to detect blood phenylalanine and tyrosine concentrations
(2) urine analysis of organic acids by gas chromatography mass spectrometry (GC / Mass)
(3) high performance liquid chromatography quantitative urine neopterin (Neopterin) and biopterin (Biopterin), and calculate the% B = B / N + BX 100%
(4) quantitative determination of erythrocyte DHPR activity
(5) When the blood PHE> 10mg/dl, can carry out the Des BH4 loading test (BH4 loading test). Fasting given BH4 7.5mg/kg ~ 20mg/kg, 30 minutes after feeding, at 2hr, 4hr, 8hr, 24hr, 48hr were measured in blood phenylalanine concentration and proportion of urine analysis Pterins, if the value at BH4 taking PHE 4-6 hours after the resumption of normal PHE <2mg/dl, for BH4 has reactive, if not lower, compared with BH4 not reactive.
(6) BH4 deficiency Des classification:
a, if the% B of normal, and Neopterin and Biopterin content were very low, BH4 Des have the load test for the reaction, they belong to the lack of GTP-cyclohydrolase type.
b, if the% B <5, the Neopterin and high content of, BH4 Des have the load test for responders, it may belong to the absence of 6-PTS-type.
C, if the% B> 80, or normal, and high-Biopterin content, BH4 Des the load test for the partial or no response, they belong to the absence of DHPR Restore type, determination of enzyme can be used to determine the red blood cells.
Clinical symptoms:
If the substantial accumulation of phenylalanine in the body, metabolism in the human body have a lot of amphetamine after acid-related metabolites, can cause the patient's brain injury, early treatment will not have a serious mental retardation. Since the disease of the brain caused by injury are progressive in nature, so many babies born asymptomatic, at about 3-4 months after the symptoms occur only slowly. The symptoms of vomiting, skin and hair color , eczema, growth retardation, urine and body odor Khan has mycophenolate draw bear, tremor and abnormal movements. If the wait time before beginning treatment, often the brain nerve has resulted in irreparable damage to the.
Against the lack of BH4 Des type of patients, apart from the above-mentioned symptoms, but also because of the lack of BH4 to merge the central nervous system conduction material and the lack of Dopamine and serotonin, and the conduct of serious central nervous system symptoms such as muscle tension reduction, beyond the control of convulsions , severe growth retardation, infection symptoms such as easy.
Treatment and prognosis:
(1) For the lack of BH4-type patients, the restriction of dietary phenylalanine method of treatment, and can not effectively prevent the central nervous system symptoms. Single use in patients with BH4 treatment can control blood phenylalanine concentration, but not easy BH4 itself through the brain barrier and can not reach the brain for brain conduction, so that caused the lack of Dopamine and serotonin can cause intellectual and spiritual obstacles Therefore, in patients with phenylketonuria need to be complemented by special-shaped above-mentioned neurotransmitter precursors for treatment, such as: dopa (L-Dopa), HTP (5-hydroxytryptophan), etc.
(B) The principle of treatment
1, BH4 (10mg BH4 2HCl, 50mg ascorbic acid, 25mg N-acetyl-L-cysteine):
Oral BH4 (10mg/tab) to 1-5mg/kg/day dose of treatment, so that the concentration of blood phenylalanine control in the long term <2mg/dl. Medication should be an empty stomach 30 minutes before eating, not the child could be crushed after the drug dissolved in cold water mixing within 30 minutes of taking finished because of BH4 on the temperature-sensitive, is strictly prohibited when taking a hot brew Moreover due to BH4 easily and with oxygen absorption effect, it should be stored in frozen state (-20. c), the BH4 in unopened -20. Under C can be stored for more than two years, placed in sealed BH4 months at room temperature, the color will become Lunatia, but still more than 99% of the activity, but when BH4 into a dark yellow color when it no longer edible.
2,5-OH tryptophan (5-OHTP: 100mg/Oxitriptan):
After meals, oral 5-OHTP to 4-10mg/kg/day dose of treatment, to add low-dose slowly up the volume, the largest not more than the use of 10mg/kg/day, in order to avoid excessive blood pressure may be a momentary instability, gastrointestinal discomfort, such as nausea, vomiting or diarrhea and other side effects. Has the above-mentioned symptoms need arises to reduce or disable the serious symptoms when treated with steroids can be used. And shall as soon as possible contact with the specialist physician.
3, Sinemet (250mg Levodopa, 50mg Carbidopa / tab):
After meals, oral Sinemet to L-dopa 5-15mg/kg/day, Carbidopa 1-2mg/kg/day dose of treatment to low-dose slowly add up the amount of time, therefore the role of medicine quickly, so dose adjustment period should be to observe the patient's response to the efficacy and side effects, if we find that patients have cramps, trembling, restlessness of the phenomenon, it may be excessive doses, or add the results of drug too fast, if the patient has weakness, or muscle stiffness and other symptoms may arise for the amount of drugs is not enough when there is the above symptoms should contact a doctor as soon as possible with the specialist.
(C) set up the ideal blood PHE control objectives
1, BH4 synthesis lack of type (GTP cylohydrolase and 6-PTS): phe <2mg/dl
2, DHPR restore lack type: phe at 2-6mg/dl between the growth period: phe at between 2-4mg/dl
Phenylketonuria
Patients suffering from such disease a disease of infants can not effectively make use of food proteins, usually lead to severe mental retardation or death. If early detection, to give birth within three months of special diet or vitamins, then most patients can have normal intellectual development.
Currently known to have the following five different enzymes will cause a lack of metabolism phenylketonuria Machine impaired:
1. Phenylalanine hydroxylation enzyme (PAH)
2. Guanine nucleoside triphosphate cyclohydrolase enzyme hydrolysis (GTPCHI)
3. C dione tetrahydro biopterin synthase (PTPS)
4. Dihydroartemisinin acridine HD reductase (DHPR)
5. Neopterin methanol dehydration amine enzymes (PCD)
Phenylketonuria of symptoms:
1. Clinical symptoms at the beginning of the first few months of birth and will not happen.
2. The general symptoms are:
Skin and hair color , smaller head circumference, vomiting caused by the growth of undesirable, body and urine odor has mycophenolate, this still has eczema, and even twitch circumstances.
3. On the other clinical symptoms:
Mental retardation, growth retardation, vulnerability, and decreased immunity.
Phenylketonuria treatment principles:
1. Control of diet intake of phenylalanine to eat a special formula milk powder
(1) low-phenylalanine formula (such as: Lofenalac), phenylalanine-free milk (such as: phenyl-free)
(2) in accordance with the recommendations of nutritionists, consumption of low-phenylalanine foods
2. The lack of Coenzyme patients, then supplemented by drug therapy (such as: BH4, L-dopa, Folinic acid)
3. Regular assessment of serum concentrations of phenylalanine
4. Regular assessment of growth and development of the situation
Currently known to have the following five different enzymes will cause a lack of metabolism phenylketonuria Machine impaired:
1. Phenylalanine hydroxylation enzyme (PAH)
2. Guanine nucleoside triphosphate cyclohydrolase enzyme hydrolysis (GTPCHI)
3. C dione tetrahydro biopterin synthase (PTPS)
4. Dihydroartemisinin acridine HD reductase (DHPR)
5. Neopterin methanol dehydration amine enzymes (PCD)
Phenylketonuria of symptoms:
1. Clinical symptoms at the beginning of the first few months of birth and will not happen.
2. The general symptoms are:
Skin and hair color , smaller head circumference, vomiting caused by the growth of undesirable, body and urine odor has mycophenolate, this still has eczema, and even twitch circumstances.
3. On the other clinical symptoms:
Mental retardation, growth retardation, vulnerability, and decreased immunity.
Phenylketonuria treatment principles:
1. Control of diet intake of phenylalanine to eat a special formula milk powder
(1) low-phenylalanine formula (such as: Lofenalac), phenylalanine-free milk (such as: phenyl-free)
(2) in accordance with the recommendations of nutritionists, consumption of low-phenylalanine foods
2. The lack of Coenzyme patients, then supplemented by drug therapy (such as: BH4, L-dopa, Folinic acid)
3. Regular assessment of serum concentrations of phenylalanine
4. Regular assessment of growth and development of the situation
The effectiveness of drug-based treatment of phenylketonuria else
Neonatal screening in Taiwan in 74 years since the implementation of neonatal screening by Taipei Veterans General Hospital were indeed Clinic for drug-type of 12 cases of children with phenylketonuria by Rong-Yang team for many years after treatment follow-up and hair Is to replace close clinical observation of frequent lumbar puncture Detect children neurotransmitter concentration Degrees, at any time to adjust drug dosages and the use of methods, may jeopardize the child's intelligence, disease The average IQ of children up to 97, compared to overseas studies of 76 children with average IQ much higher, The treatment and research results has been the United States first-class nerve Medical journals (Archives of Neurology) Accepted, published, not only to Taiwan in the drug-based treatment of phenylketonuria outcome of a new world record Record, but also shows the effectiveness of neonatal screening in Taiwan remarkable, and rare genetic diseases outstanding
Clinical outcome.
Phenylketonuria pathogenesis lies mainly in the liver to body phenylalanine (Phenylalanine,
Phe) metabolism into tyrosine (Tyrosine, Tyr) have taken place in the process of defects, leading to amphetamine
Substantial accumulation of acid in the body, which have had a lot of toxic metabolites, resulting in brain injury
Harm. Phenylketonuria in Europe and the U.S. rate of one ten thousandth of happened, our country is about 30,000 parts per statistics
1. PKU can be divided into drug-based and Food phenylketonuria two patients with phenylketonuria need food
Have to keep on the use of strict control of the treatment of low-protein diet. The so-called low-protein diet is fish,
Meat, milk, eggs, beans, etc. are rich in high-protein food for human consumption should not only eat fruits and vegetables and carefully
Deployment of special milk formula to supplement the amino acids necessary for human body to maintain normal hair growth
Required education. But more than food-type phenylketonuria phenylketonuria rare type of drug, such patients in addition to
A has the above-mentioned errors of metabolism, at the same time the merger of the central nervous system neurotransmitter synthesis of dispensable
Lack of clinical symptoms than phenylketonuria more serious type of food, and the conductive material due to the central nervous system drugs
Supplementary material is extremely difficult, so doctors in Europe and America, also known as drug-type phenylketonuria as "malignant PKU",
Is generally believed that even if early treatment, patients may be in irreparable damage to the intelligence.
Type of drug treatment in patients with phenylketonuria greatest difficulty lies in the side effects must be added great
Neurotransmitter substances, such as: Sinemet (Nanjing heart-US) ,5-HTP (Hydroxy Tryptophan Friday)
And so on, and add the required dose of the world up to now failed conclusion. General mining in the West Country
Lumbar puncture with regular inspections, to take a patient's spinal fluid, measurement of these neurotransmitter concentration
Degree to determine the dose used; but at home parents in general more difficult to accept the frequent lumbar spine wear
Thorns, and the medical team that even if the spinal fluid concentration of nerve conduction material will not be able to correct the anti -
Should be sick of nerve conduction material needs.
For newborn screening before the onset of serious damage to the brain lead to illness, Rong-Yang team
Clinical experience has shown that foreign substances for nerve conduction supplement recommended dose may be not
Adequate, it is much higher than abroad, the use of the therapeutic dose to treat this group of patients, for fear of nerve conduction were
Quality will have serious side effects, so the medical team with patients and their parents between a hot
Line for parents to return children to the situation at any time, at any time to adjust drug dosages and the use of
2
Ways. The medical department of our children cow Daoming track since physicians from 1988 to 2000 born between 12 cases of disease
Child found to replace the frequent clinical observation of the lumbar puncture nerve conduction Detect the concentration of a substance can be
Prejudice the child's intelligence, children with average IQ as high as 97, there are many children who score has been
Out come out on top, there is one of two pairs of patients for the different egg twins, children's performance at school and even
Are better than non-ill brother.
To achieve the world's first treatment results, hidden behind a lot of behind-the-scenes hero. First of all, The Guardian
Department of Health Bureau of Health more than 20 years ago set up a sound and effective newborn screening systems, and
In the ensuing continuously for so many years of support and guidance, so that Taiwan can reach the neonatal screening
International standards. In addition, cooperation with our two neonatal screening centers - the Republic of China Wei
Health Care Foundation and the Taipei pathology center, using the highest specifications and accurate testing method. Work
Usually the expense of staff holidays, encounters positive cases will be in the shortest time possible positive and Units
North General Hospital and the collection agency contact, be sure to let each case in the shortest possible time came to Taipei Veterans General Hospital
Accepted diagnostic tests and treatment to confirm. National Yang Ming University, Kwang-Jen Hsiao and Professor Liu Zizi to help build hospital
Erect the most comprehensive diagnosis of phenylketonuria drug type flow; and our quality medical team to provide
Patients and their families up in the medical, social resources, psychological assistance and care and so on.
And really the most important hero finally, is that this group of patients tirelessly parents, their
Attentive care for children, regular medication, and medical team to reach its present stage with such
Results. Especially those born at neonatal screening in a timely manner can not be found in patients and their
Parents, although these patients have been intellectual harm and there is lot of complications, but
Since they are not giving up, are willing to regularly come to our hospital for treatment and examination, so that we in their
Serious clinical symptoms, the study to more experience, so for those in the neonatal screening
Found that patients in a timely manner to obtain a more precise outcome of the treatment.
Case prior to the implementation of neonatal screening
Jia-yu was born, it usually will cramp, or is completely unable to move, our eyes will be less likely to be
Rotation, the doctor diagnosed as caused by premature cerebral palsy. However, more symptoms of ongoing
Occur - skin eczema, cramps when the body stiffness, usually when the muscles are weak and can not self -
Others eat eat, we must rely on the feeding, so thin that the skin and bones, to the two-year-old still not walking, brother
Di Yan Xiang after birth is also the same situation. Lot of doctors told Huang mother: "You children
Not saved. "But mother will not give up yellow, and even told the doctor:" I must have saved the child,
My daughter grow up to be Miss China! . " Although Huang was reluctant to give up next, but the large treatment
Costs, it is going to bankrupt the! Fortunately, Jia-yu, at two-year-old, nine-Yan Cheung, the yellow house
Taipei Veterans General Hospital to seek treatment, diagnosis, both drug-based phenylketonuria. Take medicine two days after treatment, eye
Eye can move one month after the good yu can walk, yellow mother would like to thank God for her encountered, although both the child's intellectual impairment, but they are still alive and well, good
Yu, now 24 years old, Yan Xiang, 22-year-old.
3
Newborn screening before and after the two cases
Guo mother (do not shoot the children's positive)
Lin-lin at 77 years are born not long after birth on the hospital to inform the hospital to return to review by the
Taipei Veterans General Hospital after inspection confirmed phenylketonuria drug type. Guo said the mother have a sister-ping
Ping was born are 67, have similar symptoms. Pingping 4 ~ 5 months beginning phenomena have cramps, and thereafter every
Days cramps, eyes turned upward, the body rigid and will not speak nor walk, hair every month
Burning cold, when a doctor diagnosed as cerebral palsy. Later, Lin-lin because only found out that her sister-ping
Ping is also the drug-type phenylketonuria.
Ping-Ping, 30-year-old, are in Taiwan, neonatal screening system set up before the patients have
The situation of intellectual impairment, mental retardation are now studying in a school; 20-year-old this year, Lin-lin, at birth
That is, screening for phenylketonuria patients out, it is now a college business administration department of fresh people, both children's hair
Selective indeed different.
After the implementation of neonatal screening case
Young Mother (Do not shoot the children's positive)
Happy to greet the twins were born, but after the newborn screening found benzene Tak Tak suspected urine ketone
Disease, by the Veterans General Hospital, Chiayi referral northward to do further checks to see little body and stuck the needle body
Tube, Yang mother to tears every day face, identified as phenylketonuria, the mother not only blame Yang heaven,
Have been to blame themselves, why are there only to her children by these sufferings? Yang mother slowly accepted
The facts, and to adjust mood brave face after the determination, actively cooperate with the cow care physicians and Taipei Veterans General Hospital Human
Members of the treatment. When Tak-Tak 7 months when she found Young mother pregnant, during pregnancy in the Taipei Veterans General Hospital for
The chorion puncture, is still highly suspected phenylketonuria, because after discussions with the President was reluctant to give up child
Son, the brave decision to give birth to children. After the birth of the second mining encyclical to the Taipei Veterans General Hospital for examination to determine
Phenylketonuria, but saw his brother Tak-Tak-treatment good results, he was growing up with other small
Friend is no different. Encyclical so mining has also taken an active drug treatment, hoping that he can have a
Happy childhood.
Tak-shing primary current 5-year primary mining encyclical 4 grades, from kindergarten to primary school, their brother and sister
At the same age with the study on children are no different, even more so than the average child should be excellent, Tak-shing of the study
Grade school or even twin brother than even excellent, at the piano mining encyclical on the study are also quite talented,
Yang saw my mother and normal child growth and learning, a sincere appreciation Daoming cow physicians and Taipei-rong
Total medical team carefully take care of, as well as the Republic of China Association of congenital metabolic diseases to help.
Yang mother more phenylketonuria patients want to tell every parent, and must not abandon them, as long as with the cow
Physicians and all Tongren with the job, will be able to have a satisfactory outcome!
4
Chen mother
Yi Xuan is a pretty lively little girl, was born not long that is diagnosed as drug-type benzene urine ketone
Disease, like a bolt from the blue to know their parents, but later in the cow Daoming physician encouragement, daily time
Take medicine, Yi Xuan to normal growth. However, when two-year-old Yi Xuan, his younger brother was born, David shuen this
Take medicine when beginning to resist, she often argued brother and parents why we did not take medicine and she wanted to take medicine? This
Yi Xuan's parents made a very annoyance, do not take medicine because of drug type phenylketonuria in a significant
Impact, no drugs will appear cramps, cramps, similar to the symptoms of Parkinson's disease. After To have a younger brother must also take medicine for flu, to see his younger brother David shuen ill must take medicine on the involute Gradually the. Yi Xuan is now six years old, the medication twice a day, although occasional temper or refuse Must take medicine, but to persuade the patient under the Parent, David always come shuen Finally put the. Children - my pride - you are the world's first Who says a rare disease patients and normal people can not like
5
Phenylketonuria patients with drug-based performance NO.1
Many years ago, a group of rare congenital metabolic diseases in patients with poor parents, have witnessed their own child
Son with patients in Taiwan society neglected corner of the suffering of helpless struggling for life, and many home dumping
Dang production house in search for appropriate drugs or food, or to go abroad for medical treatment, or even forced to give up child
Son. In fact, enough of these children as long as drugs, diet controls properly, they can also be normal
Like children - grow up, work, marry, have children, as has a dazzling life.
Republic of China, congenital and metabolic diseases Friends of care is also based on the establishment of such a shape
Conditions established under the domestic for the care of patients with rare diseases have not been proper planning, so
These have the same face the same difficult experience and parents are actively seeking self-help, and professional medical
Treatment under the concerted efforts of all members, the association was set up! Our goal is to:
First, to assist patients with congenital and metabolic diseases for the National Health Insurance medicine, special food and inspection costs.
Second, encourage the drug-related diseases and special R & D and manufacture of food products.
Three, assist patients and families receiving treatment and counseling and psychological counseling.
Four, holding club, seminars introduce new knowledge and the strengthening of medical patients and patients between home
Encouraged.
Friday in support of the relevant medical research.
Clinical outcome.
Phenylketonuria pathogenesis lies mainly in the liver to body phenylalanine (Phenylalanine,
Phe) metabolism into tyrosine (Tyrosine, Tyr) have taken place in the process of defects, leading to amphetamine
Substantial accumulation of acid in the body, which have had a lot of toxic metabolites, resulting in brain injury
Harm. Phenylketonuria in Europe and the U.S. rate of one ten thousandth of happened, our country is about 30,000 parts per statistics
1. PKU can be divided into drug-based and Food phenylketonuria two patients with phenylketonuria need food
Have to keep on the use of strict control of the treatment of low-protein diet. The so-called low-protein diet is fish,
Meat, milk, eggs, beans, etc. are rich in high-protein food for human consumption should not only eat fruits and vegetables and carefully
Deployment of special milk formula to supplement the amino acids necessary for human body to maintain normal hair growth
Required education. But more than food-type phenylketonuria phenylketonuria rare type of drug, such patients in addition to
A has the above-mentioned errors of metabolism, at the same time the merger of the central nervous system neurotransmitter synthesis of dispensable
Lack of clinical symptoms than phenylketonuria more serious type of food, and the conductive material due to the central nervous system drugs
Supplementary material is extremely difficult, so doctors in Europe and America, also known as drug-type phenylketonuria as "malignant PKU",
Is generally believed that even if early treatment, patients may be in irreparable damage to the intelligence.
Type of drug treatment in patients with phenylketonuria greatest difficulty lies in the side effects must be added great
Neurotransmitter substances, such as: Sinemet (Nanjing heart-US) ,5-HTP (Hydroxy Tryptophan Friday)
And so on, and add the required dose of the world up to now failed conclusion. General mining in the West Country
Lumbar puncture with regular inspections, to take a patient's spinal fluid, measurement of these neurotransmitter concentration
Degree to determine the dose used; but at home parents in general more difficult to accept the frequent lumbar spine wear
Thorns, and the medical team that even if the spinal fluid concentration of nerve conduction material will not be able to correct the anti -
Should be sick of nerve conduction material needs.
For newborn screening before the onset of serious damage to the brain lead to illness, Rong-Yang team
Clinical experience has shown that foreign substances for nerve conduction supplement recommended dose may be not
Adequate, it is much higher than abroad, the use of the therapeutic dose to treat this group of patients, for fear of nerve conduction were
Quality will have serious side effects, so the medical team with patients and their parents between a hot
Line for parents to return children to the situation at any time, at any time to adjust drug dosages and the use of
2
Ways. The medical department of our children cow Daoming track since physicians from 1988 to 2000 born between 12 cases of disease
Child found to replace the frequent clinical observation of the lumbar puncture nerve conduction Detect the concentration of a substance can be
Prejudice the child's intelligence, children with average IQ as high as 97, there are many children who score has been
Out come out on top, there is one of two pairs of patients for the different egg twins, children's performance at school and even
Are better than non-ill brother.
To achieve the world's first treatment results, hidden behind a lot of behind-the-scenes hero. First of all, The Guardian
Department of Health Bureau of Health more than 20 years ago set up a sound and effective newborn screening systems, and
In the ensuing continuously for so many years of support and guidance, so that Taiwan can reach the neonatal screening
International standards. In addition, cooperation with our two neonatal screening centers - the Republic of China Wei
Health Care Foundation and the Taipei pathology center, using the highest specifications and accurate testing method. Work
Usually the expense of staff holidays, encounters positive cases will be in the shortest time possible positive and Units
North General Hospital and the collection agency contact, be sure to let each case in the shortest possible time came to Taipei Veterans General Hospital
Accepted diagnostic tests and treatment to confirm. National Yang Ming University, Kwang-Jen Hsiao and Professor Liu Zizi to help build hospital
Erect the most comprehensive diagnosis of phenylketonuria drug type flow; and our quality medical team to provide
Patients and their families up in the medical, social resources, psychological assistance and care and so on.
And really the most important hero finally, is that this group of patients tirelessly parents, their
Attentive care for children, regular medication, and medical team to reach its present stage with such
Results. Especially those born at neonatal screening in a timely manner can not be found in patients and their
Parents, although these patients have been intellectual harm and there is lot of complications, but
Since they are not giving up, are willing to regularly come to our hospital for treatment and examination, so that we in their
Serious clinical symptoms, the study to more experience, so for those in the neonatal screening
Found that patients in a timely manner to obtain a more precise outcome of the treatment.
Case prior to the implementation of neonatal screening
Jia-yu was born, it usually will cramp, or is completely unable to move, our eyes will be less likely to be
Rotation, the doctor diagnosed as caused by premature cerebral palsy. However, more symptoms of ongoing
Occur - skin eczema, cramps when the body stiffness, usually when the muscles are weak and can not self -
Others eat eat, we must rely on the feeding, so thin that the skin and bones, to the two-year-old still not walking, brother
Di Yan Xiang after birth is also the same situation. Lot of doctors told Huang mother: "You children
Not saved. "But mother will not give up yellow, and even told the doctor:" I must have saved the child,
My daughter grow up to be Miss China! . " Although Huang was reluctant to give up next, but the large treatment
Costs, it is going to bankrupt the! Fortunately, Jia-yu, at two-year-old, nine-Yan Cheung, the yellow house
Taipei Veterans General Hospital to seek treatment, diagnosis, both drug-based phenylketonuria. Take medicine two days after treatment, eye
Eye can move one month after the good yu can walk, yellow mother would like to thank God for her encountered, although both the child's intellectual impairment, but they are still alive and well, good
Yu, now 24 years old, Yan Xiang, 22-year-old.
3
Newborn screening before and after the two cases
Guo mother (do not shoot the children's positive)
Lin-lin at 77 years are born not long after birth on the hospital to inform the hospital to return to review by the
Taipei Veterans General Hospital after inspection confirmed phenylketonuria drug type. Guo said the mother have a sister-ping
Ping was born are 67, have similar symptoms. Pingping 4 ~ 5 months beginning phenomena have cramps, and thereafter every
Days cramps, eyes turned upward, the body rigid and will not speak nor walk, hair every month
Burning cold, when a doctor diagnosed as cerebral palsy. Later, Lin-lin because only found out that her sister-ping
Ping is also the drug-type phenylketonuria.
Ping-Ping, 30-year-old, are in Taiwan, neonatal screening system set up before the patients have
The situation of intellectual impairment, mental retardation are now studying in a school; 20-year-old this year, Lin-lin, at birth
That is, screening for phenylketonuria patients out, it is now a college business administration department of fresh people, both children's hair
Selective indeed different.
After the implementation of neonatal screening case
Young Mother (Do not shoot the children's positive)
Happy to greet the twins were born, but after the newborn screening found benzene Tak Tak suspected urine ketone
Disease, by the Veterans General Hospital, Chiayi referral northward to do further checks to see little body and stuck the needle body
Tube, Yang mother to tears every day face, identified as phenylketonuria, the mother not only blame Yang heaven,
Have been to blame themselves, why are there only to her children by these sufferings? Yang mother slowly accepted
The facts, and to adjust mood brave face after the determination, actively cooperate with the cow care physicians and Taipei Veterans General Hospital Human
Members of the treatment. When Tak-Tak 7 months when she found Young mother pregnant, during pregnancy in the Taipei Veterans General Hospital for
The chorion puncture, is still highly suspected phenylketonuria, because after discussions with the President was reluctant to give up child
Son, the brave decision to give birth to children. After the birth of the second mining encyclical to the Taipei Veterans General Hospital for examination to determine
Phenylketonuria, but saw his brother Tak-Tak-treatment good results, he was growing up with other small
Friend is no different. Encyclical so mining has also taken an active drug treatment, hoping that he can have a
Happy childhood.
Tak-shing primary current 5-year primary mining encyclical 4 grades, from kindergarten to primary school, their brother and sister
At the same age with the study on children are no different, even more so than the average child should be excellent, Tak-shing of the study
Grade school or even twin brother than even excellent, at the piano mining encyclical on the study are also quite talented,
Yang saw my mother and normal child growth and learning, a sincere appreciation Daoming cow physicians and Taipei-rong
Total medical team carefully take care of, as well as the Republic of China Association of congenital metabolic diseases to help.
Yang mother more phenylketonuria patients want to tell every parent, and must not abandon them, as long as with the cow
Physicians and all Tongren with the job, will be able to have a satisfactory outcome!
4
Chen mother
Yi Xuan is a pretty lively little girl, was born not long that is diagnosed as drug-type benzene urine ketone
Disease, like a bolt from the blue to know their parents, but later in the cow Daoming physician encouragement, daily time
Take medicine, Yi Xuan to normal growth. However, when two-year-old Yi Xuan, his younger brother was born, David shuen this
Take medicine when beginning to resist, she often argued brother and parents why we did not take medicine and she wanted to take medicine? This
Yi Xuan's parents made a very annoyance, do not take medicine because of drug type phenylketonuria in a significant
Impact, no drugs will appear cramps, cramps, similar to the symptoms of Parkinson's disease. After To have a younger brother must also take medicine for flu, to see his younger brother David shuen ill must take medicine on the involute Gradually the. Yi Xuan is now six years old, the medication twice a day, although occasional temper or refuse Must take medicine, but to persuade the patient under the Parent, David always come shuen Finally put the. Children - my pride - you are the world's first Who says a rare disease patients and normal people can not like
5
Phenylketonuria patients with drug-based performance NO.1
Many years ago, a group of rare congenital metabolic diseases in patients with poor parents, have witnessed their own child
Son with patients in Taiwan society neglected corner of the suffering of helpless struggling for life, and many home dumping
Dang production house in search for appropriate drugs or food, or to go abroad for medical treatment, or even forced to give up child
Son. In fact, enough of these children as long as drugs, diet controls properly, they can also be normal
Like children - grow up, work, marry, have children, as has a dazzling life.
Republic of China, congenital and metabolic diseases Friends of care is also based on the establishment of such a shape
Conditions established under the domestic for the care of patients with rare diseases have not been proper planning, so
These have the same face the same difficult experience and parents are actively seeking self-help, and professional medical
Treatment under the concerted efforts of all members, the association was set up! Our goal is to:
First, to assist patients with congenital and metabolic diseases for the National Health Insurance medicine, special food and inspection costs.
Second, encourage the drug-related diseases and special R & D and manufacture of food products.
Three, assist patients and families receiving treatment and counseling and psychological counseling.
Four, holding club, seminars introduce new knowledge and the strengthening of medical patients and patients between home
Encouraged.
Friday in support of the relevant medical research.
Related Issues
Introduction to Drug Products Containing Phenylalanine
The information in this table of the phe content of aspartame-containing drug products was gathered by PKU father and pharmacist, Brandon Garde, Fairhaven, MA.
The table only includes name-brand products. There are so many different generic companies producing some of these products, particularly the vitamins, that it would be nearly impossible to make a complete listing of every generic manufacturer with the amount of phenylalanine in each of their products. But these tables provide a good guideline for what kind of products might contain aspartame as a sweetener (for example, chewable vitamins), so a pharmacist has a good idea about which product labels need to be closely read. In the U.S., any non-prescription medicine will list the phe content on the outside label. This will NOT apply to herbal products since they are not regulated by the FDA. Any prescription medicine will list the Phe content in the package insert, which the pharmacist should have readily available.
Any product that targets children as its main consumer has a high likelihood of containing aspartame. The product labeling should be carefully checked. The same is true for any product that is labeled "sugar-free."
Phenylalanine content equals one half the amount of aspartame. If a products label lists the amount of aspartame in mg, divide that number by 2 and youl know how much phe is in the product. Some drug products now actually contain the phe content on the label.
Table of Drug Products Containing Phenylalanine
Remember: This is not necessarily an exhaustive list. Generic brands are not included. Check with a pharmacist of you have questions about aspartame in medicines.
1. What is Kuvan and in what form is it available?
Kuvan is sapropterin dihydrochloride, a synthetic form of a naturally occurring substance tetrahydrobiopterin (BH4). Kuvan is provided as 100 mg tablets that are to be dissolved in water or apple juice, and then taken within 15 minutes after they have been dissolved.
2. What is tetrahydrobiopterin (BH4)-responsive Phenylketonuria (PKU)?
Phenylketonuria (PKU) is an inherited disorder, in which the activity of the enzyme phenylalanine hydroxylase (PAH) is deficient. PAH helps break down phenylalanine (Phe) in the body. Phenylalanine is an amino acid that is obtained from food. Patients with PKU cannot break down Phe properly, which results in high levels of Phe in the blood. In infants and children, high blood Phe levels over time can result in mental retardation, smaller brain size, delayed speech, and other neurologic problems. In adolescents and adults, high blood Phe levels can result in problems with concentration and attention.
Patients with PKU have a large variety of changes to the PAH enzyme, so not all patients with PKU will respond to BH4. In clinical trials of patients with PKU, only 20% to 56% of these patients responded to treatment with Kuvan (called BH4-responsive PKU). Response to Kuvan was measured by the lowering of blood Phe levels with Kuvan treatment.
3. How prevalent is it in American society?
One in 12,000 to 15,000 infants in the United States is born with PKU.
4. Which race or ethnic group is it seen most in?
In the United States, PKU is more common in Caucasians (approximately 1 in 8,000 babies), and is less common, for example, in African Americans (approximately 1 in 50,000).
5. How do you know if your newborn or child has the disease?
All states in the United States perform newborn screening testing for PKU at birth. You will be notified if your child’s screening test for PKU is positive.
6. Are parents carriers of this genetic disorder?
Yes. Children must inherit one copy of the defective gene for PKU from each parent. Children only show signs of PKU if they inherit a defective copy from each parent.
7. What goes wrong to cause this disease? Does lack of prenatal care cause it?
PKU is an inherited disease, where both copies of the gene must be defective to show signs of the disease. People cannot “develop” PKU later in life; they must be born with it. Lack of prenatal care has no effect on having PKU.
8. Is Kuvan the only treatment for PKU disease?
No. All patients with PKU must be treated with a low-Phe diet, and most patients will also be treated with low-Phe medical foods and formulas. For all patients, monitoring of blood Phe levels must be performed regularly by medical specialists familiar with the treatment of PKU. Patients who are taking Kuvan still need to be managed with a low-Phe diet, and have regular monitoring of their blood Phe levels.
9. How does Kuvan work?
Kuvan is a synthetic form of BH4. BH4 is a cofactor for the enzyme PAH. The enzyme PAH cannot function properly without BH4. In some patients with PKU, giving BH4 as Kuvan increases the activity of the enzyme PAH. Not all patients with PKU will respond to Kuvan. The only way to know if a patient will respond is to Kuvan is to give the patient Kuvan and monitor his/her blood Phe levels.
10. Why must you be on a restricted diet?
High levels of Phe in the diet can over-ride the effects of Kuvan on blood Phe levels. All patients taking Kuvan must continue to follow a Phe-restricted diet and have their blood Phe levels monitored by medical personnel trained in the management of PKU.
11. What types of foods should you avoid? How does one distinguish between a food that is high, low or absent of phenylalanine?
Phenylalanine is present in foods that contain proteins, such as meats, dairy, and eggs. All patients with PKU should be working with a dietician knowledgeable about PKU to help control their diet.
12. What are the symptoms of this disease?
PKU is diagnosed by special medical blood testing, and by newborn screening testing at birth. The signs and symptoms of PKU develop over time after high blood Phe levels have been present for weeks to months, or longer. In infants and children, high blood Phe levels over time can result in mental retardation, smaller brain size, delayed speech, and other neurologic problems. In adolescents and adults, high blood Phe levels can results in problems with concentration and attention.
13. Can PKU’s effects be reversed by Kuvan and a regulated diet?
No. Once neurologic problems, such as mental retardation, have developed, they cannot be reversed by Kuvan or a regulated diet. The goal of treatment with Kuvan and diet is to prevent neurologic problems from developing.
14. Why is BioMarin establishing a general disease registry for PKU? What is the purpose of it?
PKU is a rare disease, and only a small number of people in the United States (and the world) have it. The purpose of the registry is to provide a way for physicians, the FDA, and BioMarin to monitor the safety and effectiveness of Kuvan over a long period of time in as many patients as possible.
15. Why is it important to check your Phe levels in your blood?
The complications of PKU are a result of high blood Phe levels over time (for example, weeks to months, or longer). It has been shown in clinical studies conducted in patients with PKU that keeping blood Phe levels at recommended levels decreases the neurologic problems that can develop with PKU. Neither Kuvan nor following a low-Phe diet can cure PKU, but PKU can be managed. Therefore, monitoring of blood Phe levels and a low-Phe diet will need to occur over the life of the patient.
16. Can someone die from PKU disease?
Yes, but this would be due to the severe neurologic complications of PKU that develop over long periods of time. More typically, neurologic problems, such as lowered intelligence, can develop with PKU.
17. How will this drug therapy alter the quality of a PKU patients’ life?
It is hoped that the lowering of blood Phe levels in with patients BH4-responsive PKU would result in fewer neurologic complications of PKU over time, and that patients with BH4-responsive PKU who are taking Kuvan would have an easier time controlling their blood Phe levels. However, long-term studies of neurologic development have not been done with Kuvan.
18. What are the side effects of Kuvan?
The most common side effects of Kuvan were headache, vomiting, diarrhea, runny nose, cough, and sore throat. Most of these side effects were mild, and did not result in patients stopping Kuvan treatment.
19. How often should I see a doctor if I am on Kuvan and what type of doctor should I see for my PKU disease?
All patients with PKU should be treated by a medical doctor knowledgeable in the treatment of PKU, such as a Medical Geneticist. Your pediatrician or regular doctor can refer you to a specialist. Your specialist will determine how often you will need to be seen.
The information in this table of the phe content of aspartame-containing drug products was gathered by PKU father and pharmacist, Brandon Garde, Fairhaven, MA.
The table only includes name-brand products. There are so many different generic companies producing some of these products, particularly the vitamins, that it would be nearly impossible to make a complete listing of every generic manufacturer with the amount of phenylalanine in each of their products. But these tables provide a good guideline for what kind of products might contain aspartame as a sweetener (for example, chewable vitamins), so a pharmacist has a good idea about which product labels need to be closely read. In the U.S., any non-prescription medicine will list the phe content on the outside label. This will NOT apply to herbal products since they are not regulated by the FDA. Any prescription medicine will list the Phe content in the package insert, which the pharmacist should have readily available.
Any product that targets children as its main consumer has a high likelihood of containing aspartame. The product labeling should be carefully checked. The same is true for any product that is labeled "sugar-free."
Phenylalanine content equals one half the amount of aspartame. If a products label lists the amount of aspartame in mg, divide that number by 2 and youl know how much phe is in the product. Some drug products now actually contain the phe content on the label.
Table of Drug Products Containing Phenylalanine
Remember: This is not necessarily an exhaustive list. Generic brands are not included. Check with a pharmacist of you have questions about aspartame in medicines.
1. What is Kuvan and in what form is it available?
Kuvan is sapropterin dihydrochloride, a synthetic form of a naturally occurring substance tetrahydrobiopterin (BH4). Kuvan is provided as 100 mg tablets that are to be dissolved in water or apple juice, and then taken within 15 minutes after they have been dissolved.
2. What is tetrahydrobiopterin (BH4)-responsive Phenylketonuria (PKU)?
Phenylketonuria (PKU) is an inherited disorder, in which the activity of the enzyme phenylalanine hydroxylase (PAH) is deficient. PAH helps break down phenylalanine (Phe) in the body. Phenylalanine is an amino acid that is obtained from food. Patients with PKU cannot break down Phe properly, which results in high levels of Phe in the blood. In infants and children, high blood Phe levels over time can result in mental retardation, smaller brain size, delayed speech, and other neurologic problems. In adolescents and adults, high blood Phe levels can result in problems with concentration and attention.
Patients with PKU have a large variety of changes to the PAH enzyme, so not all patients with PKU will respond to BH4. In clinical trials of patients with PKU, only 20% to 56% of these patients responded to treatment with Kuvan (called BH4-responsive PKU). Response to Kuvan was measured by the lowering of blood Phe levels with Kuvan treatment.
3. How prevalent is it in American society?
One in 12,000 to 15,000 infants in the United States is born with PKU.
4. Which race or ethnic group is it seen most in?
In the United States, PKU is more common in Caucasians (approximately 1 in 8,000 babies), and is less common, for example, in African Americans (approximately 1 in 50,000).
5. How do you know if your newborn or child has the disease?
All states in the United States perform newborn screening testing for PKU at birth. You will be notified if your child’s screening test for PKU is positive.
6. Are parents carriers of this genetic disorder?
Yes. Children must inherit one copy of the defective gene for PKU from each parent. Children only show signs of PKU if they inherit a defective copy from each parent.
7. What goes wrong to cause this disease? Does lack of prenatal care cause it?
PKU is an inherited disease, where both copies of the gene must be defective to show signs of the disease. People cannot “develop” PKU later in life; they must be born with it. Lack of prenatal care has no effect on having PKU.
8. Is Kuvan the only treatment for PKU disease?
No. All patients with PKU must be treated with a low-Phe diet, and most patients will also be treated with low-Phe medical foods and formulas. For all patients, monitoring of blood Phe levels must be performed regularly by medical specialists familiar with the treatment of PKU. Patients who are taking Kuvan still need to be managed with a low-Phe diet, and have regular monitoring of their blood Phe levels.
9. How does Kuvan work?
Kuvan is a synthetic form of BH4. BH4 is a cofactor for the enzyme PAH. The enzyme PAH cannot function properly without BH4. In some patients with PKU, giving BH4 as Kuvan increases the activity of the enzyme PAH. Not all patients with PKU will respond to Kuvan. The only way to know if a patient will respond is to Kuvan is to give the patient Kuvan and monitor his/her blood Phe levels.
10. Why must you be on a restricted diet?
High levels of Phe in the diet can over-ride the effects of Kuvan on blood Phe levels. All patients taking Kuvan must continue to follow a Phe-restricted diet and have their blood Phe levels monitored by medical personnel trained in the management of PKU.
11. What types of foods should you avoid? How does one distinguish between a food that is high, low or absent of phenylalanine?
Phenylalanine is present in foods that contain proteins, such as meats, dairy, and eggs. All patients with PKU should be working with a dietician knowledgeable about PKU to help control their diet.
12. What are the symptoms of this disease?
PKU is diagnosed by special medical blood testing, and by newborn screening testing at birth. The signs and symptoms of PKU develop over time after high blood Phe levels have been present for weeks to months, or longer. In infants and children, high blood Phe levels over time can result in mental retardation, smaller brain size, delayed speech, and other neurologic problems. In adolescents and adults, high blood Phe levels can results in problems with concentration and attention.
13. Can PKU’s effects be reversed by Kuvan and a regulated diet?
No. Once neurologic problems, such as mental retardation, have developed, they cannot be reversed by Kuvan or a regulated diet. The goal of treatment with Kuvan and diet is to prevent neurologic problems from developing.
14. Why is BioMarin establishing a general disease registry for PKU? What is the purpose of it?
PKU is a rare disease, and only a small number of people in the United States (and the world) have it. The purpose of the registry is to provide a way for physicians, the FDA, and BioMarin to monitor the safety and effectiveness of Kuvan over a long period of time in as many patients as possible.
15. Why is it important to check your Phe levels in your blood?
The complications of PKU are a result of high blood Phe levels over time (for example, weeks to months, or longer). It has been shown in clinical studies conducted in patients with PKU that keeping blood Phe levels at recommended levels decreases the neurologic problems that can develop with PKU. Neither Kuvan nor following a low-Phe diet can cure PKU, but PKU can be managed. Therefore, monitoring of blood Phe levels and a low-Phe diet will need to occur over the life of the patient.
16. Can someone die from PKU disease?
Yes, but this would be due to the severe neurologic complications of PKU that develop over long periods of time. More typically, neurologic problems, such as lowered intelligence, can develop with PKU.
17. How will this drug therapy alter the quality of a PKU patients’ life?
It is hoped that the lowering of blood Phe levels in with patients BH4-responsive PKU would result in fewer neurologic complications of PKU over time, and that patients with BH4-responsive PKU who are taking Kuvan would have an easier time controlling their blood Phe levels. However, long-term studies of neurologic development have not been done with Kuvan.
18. What are the side effects of Kuvan?
The most common side effects of Kuvan were headache, vomiting, diarrhea, runny nose, cough, and sore throat. Most of these side effects were mild, and did not result in patients stopping Kuvan treatment.
19. How often should I see a doctor if I am on Kuvan and what type of doctor should I see for my PKU disease?
All patients with PKU should be treated by a medical doctor knowledgeable in the treatment of PKU, such as a Medical Geneticist. Your pediatrician or regular doctor can refer you to a specialist. Your specialist will determine how often you will need to be seen.
Disease Management
PKU is monitored with three main tools:
monthly blood phe levels
regular visits to the PKU Clinic
monthly food records
Monthly blood tests help people with PKU track their progress with the diet. These blood tests measure phe build-up in the blood. (High levels indicate too much phe from food or too little Phenyl-Free*.) People with PKU should keep their blood phe levels in the safe range, between 1 and 6 mg/dL.
Regular measurement of blood phe levels can be done in 2 ways:
a blood draw in a hospital or clinic, which directly measures phe in the blood
a collection of a blood sample on a filter paper at home, which is mailed to the laboratory for analysis
Regular visits to the PKU clinic are an important opportunity for people with PKU to meet with the PKU team. During these visits, everyone on the team works together to give the best possible care and guidance for people with PKU. The visit should include a blood draw, a short exam by a pediatrician, and a chance to discuss ways to manage the low-phe food pattern. The nutrition education activity for children and parent support group for families are important components of the clinic visit at the University of Washington.
Food records are usually a 3 day diary of all foods and beverages eaten and the amounts consumed. These diaries should be accurate records of foods eaten. They will help the PKU clinic team to interpret blood phe levels and make adjustments to the food and formula prescription.
* Phenyl-Free is a registered trademark of Mead Johnson Co. A number of other formulas are available.
NIH Consensus Panel Recommends Comprehensive Approach to Life Long Care for PKU
People with the rare metabolic disorder phenylketonuria need to adhere to the special diet central to their treatment, concluded a Consensus Panel convened by the National Institutes of Health. The conclusion addresses a long-standing difference of opinion about whether people with phenylketonuria could abandon the diet after early childhood.
Phenylketonuria (PKU) is an inherited disorder that, if untreated, causes profound mental retardation as well as other medical problems. The disorder, which affects about one of every 15,000 infants in the United States, usually results from a deficiency of an enzyme known as phenylalanine hydroxylase. This deficiency leads to elevated levels of the amino acid phenylalanine (Phe) in the bloodstream. Screening newborn infants for PKU is standard practice throughout many parts of the world.
"As a result of the screening programs that began nearly 40 years ago, thousands of children with PKU have been identified and treated," said R. Rodney Howell, M.D. Chairman of the Consensus Panel. "Most of these children have grown into healthy adults when they would otherwise have developed mental retardation and other problems associated with PKU."
The current treatment for PKU involves dietary modification and generally excludes all high protein foods, such as meat, milk, eggs, and nuts, since all protein contains phenylalanine. Bread and other wheat products also are excluded. The diet includes special Phe-free foods that supply nutrients that the restrictive food choices lack.
The panel stressed that the dietary control of PKU is only one component of a lifelong treatment program, which should include frequent blood tests, daily dietary logs, and regular, frequent visits to a PKU clinic.
"Although we've made enormous gains, we need to assure that everyone has access to culturally sensitive age-appropriate treatment programs," Dr. Howell added.
The panel issued its statement at the conclusion of a 3-day NIH Consensus Development Conference on Phenylketonuria (PKU): Screening and Management. The conference, held October 16-18, 2000 at the NIH, brought together national and international experts to present the latest research findings on PKU epidemiology and genetics, screening strategies, and treatment regimens.
The panel also recommended beginning treatment for all newborns with the disorder within 7 -10 days after birth to reduce Phe levels as rapidly as possible. In addition, the panel agreed upon target phenylalanine levels for infants and children through 12 years (2-6 mg/dl) and for individuals over age 12 (2-15 mg/dl). Noting the limited data available on the relationship between Phe level and brain function after 12 years of age, and the fact that brain development continues during adolescence, the panel encouraged even lower Phe levels (2-10 mg/dl) during this age period.
Panelists underscored the importance of controlling Phe levels in women of childbearing age with PKU. Non-PKU children exposed to high levels of Phe in the womb are vulnerable to mental retardation, congenital heart disease, and other disorders.
The panel called for uniform policies to remove the individual and the family financial barriers to medical foods, modified low-protein foods, and access to support services required to maintain appropriate Phe levels. Panel members also called for a comprehensive, integrated system to deliver care to people with the disorder, consistency among screening, treatment, and data collection and patient support programs. Currently there is variation regarding newborn screening practice in the United States as well as for criteria defining positive PKU tests.
Panel members also noted that dietary restrictions can be difficult to follow, and dietary nonadherence can result in decline of mental and behavioral performance. For this reason, the panel called for research to examine a wide range of potential new treatments other than dietary therapy. These might include the development of drugs to break down Phe as well as investigating the possibility of gene therapy to replace the defective enzyme in PKU.
The NIH Office of Medical Applications of Research and the National Institute of Child Health and Human Development sponsored the conference. Cosponsors included the National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Nursing Research, and the Maternal and Child Health Bureau of the Health Resources and Services Administration.
The full NIH Consensus Statement on Phenylketonuria (PKU): Screening and Management is available by calling 1-888-NIH-CONSENSUS (1-888-644-2667) or by visiting the NIH Consensus Development Program Web site at http://consensus.nih.gov.
The consensus statement is the report of an independent panel and is not a policy statement of the NIH or the Federal Government. The NIH Consensus Development Program was established in 1977 to resolve in an unbiased manner controversial topics in medicine. To date, NIH has conducted 112 such conferences addressing a wide range of controversial medical issues important to health care providers, patients, and the general public.
monthly blood phe levels
regular visits to the PKU Clinic
monthly food records
Monthly blood tests help people with PKU track their progress with the diet. These blood tests measure phe build-up in the blood. (High levels indicate too much phe from food or too little Phenyl-Free*.) People with PKU should keep their blood phe levels in the safe range, between 1 and 6 mg/dL.
Regular measurement of blood phe levels can be done in 2 ways:
a blood draw in a hospital or clinic, which directly measures phe in the blood
a collection of a blood sample on a filter paper at home, which is mailed to the laboratory for analysis
Regular visits to the PKU clinic are an important opportunity for people with PKU to meet with the PKU team. During these visits, everyone on the team works together to give the best possible care and guidance for people with PKU. The visit should include a blood draw, a short exam by a pediatrician, and a chance to discuss ways to manage the low-phe food pattern. The nutrition education activity for children and parent support group for families are important components of the clinic visit at the University of Washington.
Food records are usually a 3 day diary of all foods and beverages eaten and the amounts consumed. These diaries should be accurate records of foods eaten. They will help the PKU clinic team to interpret blood phe levels and make adjustments to the food and formula prescription.
* Phenyl-Free is a registered trademark of Mead Johnson Co. A number of other formulas are available.
NIH Consensus Panel Recommends Comprehensive Approach to Life Long Care for PKU
People with the rare metabolic disorder phenylketonuria need to adhere to the special diet central to their treatment, concluded a Consensus Panel convened by the National Institutes of Health. The conclusion addresses a long-standing difference of opinion about whether people with phenylketonuria could abandon the diet after early childhood.
Phenylketonuria (PKU) is an inherited disorder that, if untreated, causes profound mental retardation as well as other medical problems. The disorder, which affects about one of every 15,000 infants in the United States, usually results from a deficiency of an enzyme known as phenylalanine hydroxylase. This deficiency leads to elevated levels of the amino acid phenylalanine (Phe) in the bloodstream. Screening newborn infants for PKU is standard practice throughout many parts of the world.
"As a result of the screening programs that began nearly 40 years ago, thousands of children with PKU have been identified and treated," said R. Rodney Howell, M.D. Chairman of the Consensus Panel. "Most of these children have grown into healthy adults when they would otherwise have developed mental retardation and other problems associated with PKU."
The current treatment for PKU involves dietary modification and generally excludes all high protein foods, such as meat, milk, eggs, and nuts, since all protein contains phenylalanine. Bread and other wheat products also are excluded. The diet includes special Phe-free foods that supply nutrients that the restrictive food choices lack.
The panel stressed that the dietary control of PKU is only one component of a lifelong treatment program, which should include frequent blood tests, daily dietary logs, and regular, frequent visits to a PKU clinic.
"Although we've made enormous gains, we need to assure that everyone has access to culturally sensitive age-appropriate treatment programs," Dr. Howell added.
The panel issued its statement at the conclusion of a 3-day NIH Consensus Development Conference on Phenylketonuria (PKU): Screening and Management. The conference, held October 16-18, 2000 at the NIH, brought together national and international experts to present the latest research findings on PKU epidemiology and genetics, screening strategies, and treatment regimens.
The panel also recommended beginning treatment for all newborns with the disorder within 7 -10 days after birth to reduce Phe levels as rapidly as possible. In addition, the panel agreed upon target phenylalanine levels for infants and children through 12 years (2-6 mg/dl) and for individuals over age 12 (2-15 mg/dl). Noting the limited data available on the relationship between Phe level and brain function after 12 years of age, and the fact that brain development continues during adolescence, the panel encouraged even lower Phe levels (2-10 mg/dl) during this age period.
Panelists underscored the importance of controlling Phe levels in women of childbearing age with PKU. Non-PKU children exposed to high levels of Phe in the womb are vulnerable to mental retardation, congenital heart disease, and other disorders.
The panel called for uniform policies to remove the individual and the family financial barriers to medical foods, modified low-protein foods, and access to support services required to maintain appropriate Phe levels. Panel members also called for a comprehensive, integrated system to deliver care to people with the disorder, consistency among screening, treatment, and data collection and patient support programs. Currently there is variation regarding newborn screening practice in the United States as well as for criteria defining positive PKU tests.
Panel members also noted that dietary restrictions can be difficult to follow, and dietary nonadherence can result in decline of mental and behavioral performance. For this reason, the panel called for research to examine a wide range of potential new treatments other than dietary therapy. These might include the development of drugs to break down Phe as well as investigating the possibility of gene therapy to replace the defective enzyme in PKU.
The NIH Office of Medical Applications of Research and the National Institute of Child Health and Human Development sponsored the conference. Cosponsors included the National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Nursing Research, and the Maternal and Child Health Bureau of the Health Resources and Services Administration.
The full NIH Consensus Statement on Phenylketonuria (PKU): Screening and Management is available by calling 1-888-NIH-CONSENSUS (1-888-644-2667) or by visiting the NIH Consensus Development Program Web site at http://consensus.nih.gov.
The consensus statement is the report of an independent panel and is not a policy statement of the NIH or the Federal Government. The NIH Consensus Development Program was established in 1977 to resolve in an unbiased manner controversial topics in medicine. To date, NIH has conducted 112 such conferences addressing a wide range of controversial medical issues important to health care providers, patients, and the general public.
Nutrition
Mealtime is important family time." We have all heard that phrase and probably sometimes wonder why it is so important, especially since families are so busy and time together is hard to come by. Is the family meal really an opportunity to improve diet and health? Or is the advantage of the family meal to develop social skills and family cohesiveness? In other words, does eating together really make a difference? We believe so!
Families whose children have PKU may think that the concept of amily meals? does not directly apply to them because not all family members are eating the same foods at a meal. But family meals are as important for PKU families as for any other familyaybe even more so, since mealtime provides not only an important opportunity for education about the diet but it reinforces the idea that food differences do not deter family togetherness.
As those of you who are a part of the PKU community know well, mealtime sometimes can be challenging for all family members. But we believe that the family meal is such an important aspect of family life that to try to answer the question posed above, and others related to family meals, we have gathered information from three sources: 1) articles in the popular press, 2) research articles by health professionals, and 3) parents of children with PKU (through a questionnaire to the PKU Listserv support group.)
Recently, the popular press has "weighed in" on the importance of family meals. For example, in a provocative Seattle Times article, Daniel Hong (1) put it this way: ould you be interested in a program for your kids that improves academic performance, reduces risky behavior, promotes physical well-being, stabilizes emotions, and eventually enhances your family relationship, all at no cost? The program is often called he wonder meal?or he miracle meal,?but I call it he real happy meal.?Hong goes on to say that this result requires "something invisibleamely, your commitment and time."
Stated this way, the family meal has an enormous impact on family life, including health and wellness. Is this promise "too good to be true?" Does the family meal really have this level of impact on the lives of our children? If we want accomplished children in our families, should we "change our ways" as soon as possible and start nightly family dinners if that is not our current practice?
Frequency of Family Meals
How often families eat a meal together depends on the age of the children in the family and the background of the family. A 1991 general telephone survey of families of children 12 to 17 years old found that about 1/4 of families ate family dinner together every day, about 1/2 of the families ate dinner together 4 to 6 times per week, and the remaining 1/4 of families ate dinner as a family 1 to 3 days per week. The frequency of family dinner decreased as the children entered their teens, twice as many 12-year-old children as 17-year- old children have dinner with their families (2).
Family background also plays an important factor in family meals. Boys were noted to sit down for a family dinner more often than girls; and of the reported family backgrounds, Asian American youth more likely to have dinner with their family, and Caucasian American youth are the least likely to do so.
Parade Magazine (3) reported on the recent Parade poll and noted that 25% of families reported eating together every night; an additional 34% of families eat together most nights. Three quarters of the families reported that they ate together on Sunday night. The Parade data suggested that 78% of families have a family dinner at least a few times a week. Also, 69% say that they enjoy the family dinner and looked forward to family meals. Twenty-five percent said family dinners are at a restaurant; and 23% wished they could have a family meal more often.
Family Meals and Nourishment
The family meal has been promoted as the foundation for healthful food choices. Over 1,700 high school students were surveyed and reported strong associations between family meals and healthful meals. For example, a greater number of family meals per week was strongly related to an increased intake of fruits and vegetables and a significantly decreased intake of soft drinks. Further, more frequent family meals indicated a higher priority in families for meal structure and social eating and this positive effect lasted into adulthood (4).
However, regardless of the source of the food, eating together enhances the nourishment of the meal. Teens in homes with fewer than three fast food family meals per week with their families were more likely to eat vegetables and milk with these meals than teens that ate fast food meals without their families (5).
Adolescents and the Importance of Family Meals
About 1,000 US adolescents and their parents were asked about their family mealtime environment. Parents ascribed a higher value to the family meal than did the adolescents. Younger adolescents were more likely to eat with their families than older adolescents. The older adolescents reported that they enjoyed the family meal, but scheduling conflicts interfered with eating with their family regularly (6).
The family meal seems to have a powerful developmental role beyond food and nourishment. In research language, the frequency of family dinner is an xternal developmental assessment?or rotective factor? that may curtail high-risk behaviors among youth. In other words, among the nearly 100,000 6th to 12th grade students who were surveyed, with consideration for differing family constellations, the more frequently the family had dinner together the less often the adolescent engaged in high-risk behaviors. The high-risk behaviors measured included substance use, sexual activity, depression/suicide, violence, antisocial behaviors, school problems, and binge eating/purging (7). For younger kids ( middle school age) family meals were also a protective factor that supported the development of communication skills and led to greater academic success (8).
Family Meals and Television Watching
Perhaps a less powerful but important aspect of family meals is whether the television is on or off during the meal. The more hours a preschool age child watches television while eating, the greater the liklihood that they will consume more food (9). Children who watched more television and ate fewer family meals were more likely to be overweight by the third grade. (10). The quality of the family dinner appears to be influenced by whether or not the television is turned on. Each night that the family ate dinner together was positively associated with serving fruits or vegetables at the meal. Serving fruits or vegetables decreased with each night the television was on during dinner (11). Teens also reported poorer nutritional intake during family meals that included television watching (12).
However, watching television during family meals was associated with a more healthful diet than not eating regular family meals at all. The biggest factor is not whether the TV is on or off, but whether the family is eating a meal together. Children and teens eat better quality food when they are not alone.
Overall Benefits of Family Meals
Nutrition researchers have long been interested in the family meal and its impact on the health and well-being of children. Eating meals as a family can actually improve children food habits and nutrient intake; parents can model the social behavior they expect; and children and teens will develop social skills and behaviors. We learn our food preferences, our pace of eating, our interaction with others, and our habits of activity at a very young age. Sitting down to dinner with your family will help family members eat a more healthful diet, develop social skills, and possibly avoid high-risk behaviors. In summary, mealtime is important family time. The most important part of family mealtime is simplet the family being together.
Getting Started
It never too early to start having regular family meals, especially since young children want to try what their parents and older siblings eat. Pull the high chair to the table with the rest of the family, even though the infant may only have a few finger foods. Start slowerhaps weekend breakfasts with toddlers might be more relaxed. For preschool children, include foods they like as well as new ones (with you modeling eating and enjoying the ew?food); turn off the TV.
School age children often enjoy helping with the food preparation or setting the table; they like making meals pecial?with candles, place mats, etc; and they can be expected to carry on a conversation. Family meals don have to be elaborate or even have hot foodst being together that counts.
Infants, children and adolescents all depend on regular meals. Regular meals provide the sense to children that their basic needs will be taken care of and that others care about them. Foods offered only when your child asks for something to eat are not considered to be a family meal.
What in some families is called elpy-selfy?is alright as an occasional event, but does not meet emotional, developmental, or nourishment needs when it is a regular practice at the exclusion of family meals.
If you present meals at a more or less regular time and offer a variety of food in a pleasant and matter-of-fact way, your child will grow up to like a range and variety of foods. Your child will also be comfortable and self-assured about choosing appropriate PKU-friendly foods in a variety of social and community settings. Regular family meals and the social interaction they provide are essential for helping your child or adolescent choose to eat the right amount and type of foods to get the body that is right for him or herot too fat, not too thin, but just right and with excellent blood phe levels!
Meal Practices Among PKU Families
On the PKU Listserv, we asked members to tell us about their family meals. Many of you responded with very thoughtful answers and we thank you for sharing with the PKU community. In fact, your responses were so generous that printing all of them would take many more pages than we have available in the newsletter. So we will share some that are representative of the group.
Your responses reflected the ages of your children; whether or not you lived in a rural or urban area, family employment and schedules, and the willingness to include a variety of meal needs into the family meal. This diversity of family situations, while maintaining a commitment to the family meal, we found to be heartwarming.
Making family meals a priority and creating the expectation of regular family meals
More than half of the people who responded reported that the family had an evening meal together six or more times per week; another one third noted they had dinner together 4-5 times/week. Typical responses were:
We try to eat dinner together at home every night during the week. It doesn always happen with school and activities, but it is our goal.
Usually we eat all together as a family at the dinner table since this is the best time we can really be together and go over the days?events.
The only time we don eat together is during sports season because of practice and game times. If one child is absent we still have a family meal. We usually have the TV off for our dinner meal.
We have tried to make family mealtime very important from the beginning. Whether our young son is eating with us or not, we always have him sit in his highchair.
Family Meal Preparation and Encouraging Responsibility
Who prepares the meals at home most often?
Mom won in this category ?hands down.?Most families report that mom plans the meals and prepares most of the food for the entire family. Wonderfully, many families have shared cooking responsibilities, which includes all of the children in the family. Kids have a variety of responsibilities depending on age, skills, and number of children in the family. Typical responses were:
I am responsible for meal planning and preparation; my children help me select some options, such as vegetables, or choosing one of two different meal options. They also set the table and clear their dishes.
Both my husband and I work, so in order to minimize stress I try to plan out the meals ahead of time. Whatever we eat I try to incorporate a similar meal for her as well. For example, if we have spaghetti, then she has spaghetti. I realize she has specific dietary needs but our meals can resemble one another if it is possible.
My son loves to help in the kitchen. I have a few special kid knives purchased from Pampered Chef so he can help with the cutting of veggies/breads, etc. He loves to saut?foods on the stove and helps bake and mix batters for me. He is a super help in the kitchen, even when it comes to cleaning up!
My 16 year-old daughter helps with food preparation. She will peel vegetables, cut up onions, whatever I ask her to do. Also, if I have planned something for my husband and myself that she cannot have, she will prepare something for herself.
My daughter loves to help with dinner. Shel cut veggies for me, like carrots or celery. If we have mashed potatoes, she gets to do the mashing. When we have grilled cheese and tomato soup, she is always in charge of the sandwiches. Her grilled cheese consists of a slice of low pro bread, buttered on both sides and grilled. She also makes the regular grilled cheese. If I not home to make dinner she will generally make her own. She usually makes pasta or rice, soup and sandwiches.
How Do PKU Families Manage Eating Out?
Again, family practice depends on age of child or children, family resources, and location. Some families eat out very seldom; about 40% of families reported that they eat out frequentlyt least once or twice a week; and another one-third noted that they eat out from once to three times per month.
Typical responses were from families who have developed innovative ways to include all family members in a o fuss?manner.
We usually eat out together about 1 or 2 times a week and we try to make Sunday dinner a tradition at Grammy house.
We usually go out to eat once or twice each week. We try to either go someplace that has items my son can eat or else we take special items for him to eat.
We eat out approximately 3 times a month. With my son being older, he usually orders the buffet so he can get the salad and a baked potato.
We eat ake-out?or in a restaurant about 2-4 times/month and have found which restaurants have microwaves and have learned which have PKU-friendly menus.
Summary of PKU Family Responses
In the PKU community, the family meal seems to be live and well,? at least among families who responded to our questionaire. Families and their children are flexible and creative in providing a healthy and supportive family environment for all of their children.
Based on the research reviewed here and the testimony of listserv members, there are many ways to achieve family togetherness and a healthy family meal. Family togetherness and family role modeling appears to be a more powerful motivation for the family meal than the food. The habits of eating together developed in childhood will continue to support good health into adulthood.
Parents?Most Important Role
From the very beginning, parents and family members model important roles for children. The adults in a child life model what to do, what not to do, and how to handle daily life. This modeling plays a very important role in a child growth and development and sets the tone for children behavior. If a parent is a positive role model for healthy food choices, regular meals, and physical activity habits, children are more willing and more likely to do the same.
As a parent it is often easier to promote the axiom o as I say?instead of o as I do.? Parents whose children have PKU may find themselves drawn to an authoritative approach to food and eating because of the prescribed parameters of food and medical food intake. This type of authoritative parenting can work against successful nourishment and parenting interactions around food choices. Many children will see the emand?that a certain food be eaten at a certain time as a urf atter and many will rebel and refuse the food. On the other hand, modeling positive behaviors teaches children about appropriate foods choices, and appropriate portion sizes of foods without the authoritative approach. It also emphasizes shared responsibility for nourishment and behavior; that is, everyone in the family has a role in the family meal (for example, food preparation, choosing the amount of food to eat, clearing the dishes from the table).
The PKU families in our survey noted that positive strategies for meals in their family included: offering food with a positive, but neutral tone; offering a choice of fruits and vegetables for all family members at meals; assuring that each family member had appropriate ilk?to drink at each meal; having a regular rotation among family members in choosing the vegetable or, perhaps, the dessert for the meal; and assuring that each person in the family had an age and skill appropriate role in the meal preparation and clean-up. Children who are actively involved with their families in any aspect of the family meal have a head start on developing self-confidence in social situations outside of the immediate family.
Resources
A valuable resource for families and health care professionals alike is the Bright Futures series of materials at www.brightfutures.aap.org (American Academy of Pediatrics). Bright Futures: Guidelines for Health Supervision of Infants, Children, and Adolescents was developed to provide comprehensive health supervision and parent guidelines with detailed anticipatory guidance for ages and stages of development. Bright Futures provides guidelines that focus on physical activity, nourishment, and health behaviors for each age and stage.
Another important resource is Ellyn Satter (www.ellynsatter.com), a nutritionist who has researched and taught about the importance of family meals for decades. She provides some essential concepts that apply to all family members, regardless of health status. A monthly newsletter (Family Meals Focus) and well-researched guidelines are provided at www.ellynsatter.com/newsletter.htm.
References
1. Hong D. The Happiest Meal of All. Seattle Times, Nov 24, 2006.
2. Rockett HRH. Family Dinner: More Than Just a Meal. J Amer Diet Assoc. 107: 1498-1501, 2007.
3. Schnurnberger L. The Truth about Family Meals. Parade Magazine Nov 11, pages 10-11, 2007.
4. Larson NI et al. Family meals during Adolescence are Associated with Higher Diet Quality and Healthful Meal Patterns during Adulthood. J Amer Diet Assoc. 107: 1502-1510, 2007.
5. Boutelle KN et al. Fast food family meals: relationships with patent and adolescent food intake, home food availability and weight status. Public Health Nutr 10: 16-23, 2007.
6. Fulkerson JA et al. Adolescent and parent views of family meals. J Amer Diet Assoc 106: 526-532, 2006.
7. Fulkerson JA et al. Family dinner meal frequency and adolescent development: relationships with developmental assets and high-risk behaviors. J Adolesc Health 39: 337-345, 2006.
8. Gillman MW et al. Family dinner and diet quality among older children and adolescents. Arch Family Med 9: 235-240, 2000.
9. Francis L et al. Does Eating during television Viewing Affect Preschool Children Intake? J Amer Diet Assoc 106: 598-600, 2006.
10. Gable S et al. Television Watching and Frequency of Family Meals are Predictive of Overweight Onset and Persistence in a National Sample of School-Aged Children. J Amer Diet Assoc. 107: 53-61, 2007.
11.Fitzpatrick E et al. Positive effects of family dinner are Undone
Some have expressed concerns about the safety of aspartame, and there has been debate over whether it might be linked to a variety of symptoms and illnesses. However, based on current scientific evidence, the U.S. Food and Drug Administration (FDA) has approved aspartame as safe for kids and adults to consume. (The FDA has also approved four other artificial sweeteners: saccharine, acesulfame potassium [acesulfame-K], neotame, and sucralose.)
Government regulators in more than 100 other countries, along with independent groups such as the American Medical Association (AMA) and the World Health Organization (WHO), also have said that food and drinks containing aspartame are safe as long as they're part of a balanced diet.
The FDA does recommend that kids and adults limit how much aspartame they consume to no more than 50 milligrams of aspartame per 2.2 pound (1 kilogram) of body weight per day. The average person consumes less that 2% of this amount per day, so it would be difficult to consume harmful amounts of aspartame.
Here's a quick guide to popular products and the average amount of aspartame in each serving:
12 ounces (360 milliliters) of diet soda = 225 milligrams of aspartame
½ cup (120 milliliters) of sugar-free frozen dairy dessert (frozen yogurt, ice cream, etc.) = 47 milligrams of aspartame
1 packet of artificial sweetener = 37 milligrams of aspartame
Some people should avoid aspartame. Anyone who has the rare hereditary disease phenylketonuria (PKU) is unable to break down the compound phenylalanine, which is in aspartame. Consumption of too much aspartame can result in brain damage and cognitive impairment for anyone with PKU.
The FDA requires all products that contain artificial sweeteners to state that on the label. However, if you are concerned about your kids' aspartame consumption, talk with your doctor.
There are a number of lower phe substitutes for high protein foods. (For example,
low phe peanut butter, imitation cheese, cream cheese, and cheese sauces, and
imitation chocolate are available.) These foods are generally lower in phe than their
look-alikes, but are not free foods. Here are some things to consider when deciding
whether or not these products are right for your child with PKU. You can use these
questions to decide your approach to other “sometimes” foods too.
1. Does your child clearly understand the difference between high protein foods
and look-alike foods?
2. How BIG is your child’s appetite?
• Will he or she be satisfied with “just a little”?
• Would it be easier to have “yes” foods that could be eaten in (nearly)
unlimited amounts to satisfy his or her appetite?
3. What is your child’s “phe tolerance”?
• Is there room in your child’s food pattern to incorporate additional phe from
non-essential foods?
• What other foods are you willing to limit to include the look-alike foods?
4. Is the look-alike product acceptable? Is it readily available?
• What is the cost of the food substitute?
• Is the product acceptable with regards to appearance, taste, texture?
5. How will the look-alike food be used?
• If it will be used as a treat, will your child think that low phe foods are “not
as good” as high phe foods or look-alike foods?
• Will the look-alike food encourage/support compliance with regular use?
• Will it become another issue of “negotiation”?
What is Included in a Low Phenylalanine Food Pattern?
The diet for PKU consists of a phenylalanine-free medical formula and carefully measured amounts of fruits, vegetables, bread, pasta, and cereals. Many people who follow a low phenylalanine (phe) food pattern eat special low protein breads and pastas. They are nearly free of phe, allow greater freedom in food choices, and provide energy and variety in the food pattern.
What is Not Included in a Low Phenylalanine Food Pattern?
Foods that contain large amounts of phe must be eliminated from a low phe diet. These foods are high protein foods, such as milk, dairy products, meat, fish, chicken, eggs, beans, and nuts. These foods cause high blood phe levels for people with PKU.
Aim for Healthy Choices
This target is an easy way to visualize the foods allowed on the diet for PKU. The phenylalanine-free formula, such as Phenyl-Free*, is the center of the target diet. As the foods get further away from the bull's-eye, they are higher in phenylalanine. The foods outside the target are not included in the low-phenylalanine meal plan.
How Can This Food Pattern be Enough?
It is not unusual for someone who follows a low phe diet to have 2 kinds of vegetables and a baked potato for dinner. However, if these foods were the only foods a person consumed, his or her diet would be lacking protein, vitamins, and minerals. That is where the special formula comes in.
A special phenylalanine-free formula, such as Phenyl-Free*, contains protein, vitamins, minerals and energy (calories) with no phenylalanine. With formula, a person with PKU gets plenty of protein, without the side effects of the high phe content of most foods. The phenylalanine-free formula is the most important part of the diet for PKU.
How Long Must a Person With PKU Follow This Special Diet?
Research has shown that this diet should be followed for life. Keeping blood phe levels in the safe range helps to prevent problems with thinking and problem solving.
In the past, people with PKU were advised to stop their low phe diet when they were children. Most young people with PKU who were taken "off diet" did not monitor their blood phe levels and were not given any reason to be concerned about them. These people began to experience problems with paying attention, concentrating, and remembering. Recently, many of these same people have decided to go back "on diet" hoping to feel better. In order to go "on diet" a person must drink a special phenylalanine-free formula and choose low phe foods so that blood phe levels are in the safe range.
It is never too late to go back "on diet." A low phe diet helps most young adults with PKU to feel better and improves attention span, concentration, and memory. In general, young adults who have made these changes report that they think and feel better. The effort that it takes to bring down blood phe levels is well worth it for everyone, no matter how long they have been "off diet."
* Phenyl-Free is a registered trademark of Mead Johnson Co. A number of other formulas are available.
Families whose children have PKU may think that the concept of amily meals? does not directly apply to them because not all family members are eating the same foods at a meal. But family meals are as important for PKU families as for any other familyaybe even more so, since mealtime provides not only an important opportunity for education about the diet but it reinforces the idea that food differences do not deter family togetherness.
As those of you who are a part of the PKU community know well, mealtime sometimes can be challenging for all family members. But we believe that the family meal is such an important aspect of family life that to try to answer the question posed above, and others related to family meals, we have gathered information from three sources: 1) articles in the popular press, 2) research articles by health professionals, and 3) parents of children with PKU (through a questionnaire to the PKU Listserv support group.)
Recently, the popular press has "weighed in" on the importance of family meals. For example, in a provocative Seattle Times article, Daniel Hong (1) put it this way: ould you be interested in a program for your kids that improves academic performance, reduces risky behavior, promotes physical well-being, stabilizes emotions, and eventually enhances your family relationship, all at no cost? The program is often called he wonder meal?or he miracle meal,?but I call it he real happy meal.?Hong goes on to say that this result requires "something invisibleamely, your commitment and time."
Stated this way, the family meal has an enormous impact on family life, including health and wellness. Is this promise "too good to be true?" Does the family meal really have this level of impact on the lives of our children? If we want accomplished children in our families, should we "change our ways" as soon as possible and start nightly family dinners if that is not our current practice?
Frequency of Family Meals
How often families eat a meal together depends on the age of the children in the family and the background of the family. A 1991 general telephone survey of families of children 12 to 17 years old found that about 1/4 of families ate family dinner together every day, about 1/2 of the families ate dinner together 4 to 6 times per week, and the remaining 1/4 of families ate dinner as a family 1 to 3 days per week. The frequency of family dinner decreased as the children entered their teens, twice as many 12-year-old children as 17-year- old children have dinner with their families (2).
Family background also plays an important factor in family meals. Boys were noted to sit down for a family dinner more often than girls; and of the reported family backgrounds, Asian American youth more likely to have dinner with their family, and Caucasian American youth are the least likely to do so.
Parade Magazine (3) reported on the recent Parade poll and noted that 25% of families reported eating together every night; an additional 34% of families eat together most nights. Three quarters of the families reported that they ate together on Sunday night. The Parade data suggested that 78% of families have a family dinner at least a few times a week. Also, 69% say that they enjoy the family dinner and looked forward to family meals. Twenty-five percent said family dinners are at a restaurant; and 23% wished they could have a family meal more often.
Family Meals and Nourishment
The family meal has been promoted as the foundation for healthful food choices. Over 1,700 high school students were surveyed and reported strong associations between family meals and healthful meals. For example, a greater number of family meals per week was strongly related to an increased intake of fruits and vegetables and a significantly decreased intake of soft drinks. Further, more frequent family meals indicated a higher priority in families for meal structure and social eating and this positive effect lasted into adulthood (4).
However, regardless of the source of the food, eating together enhances the nourishment of the meal. Teens in homes with fewer than three fast food family meals per week with their families were more likely to eat vegetables and milk with these meals than teens that ate fast food meals without their families (5).
Adolescents and the Importance of Family Meals
About 1,000 US adolescents and their parents were asked about their family mealtime environment. Parents ascribed a higher value to the family meal than did the adolescents. Younger adolescents were more likely to eat with their families than older adolescents. The older adolescents reported that they enjoyed the family meal, but scheduling conflicts interfered with eating with their family regularly (6).
The family meal seems to have a powerful developmental role beyond food and nourishment. In research language, the frequency of family dinner is an xternal developmental assessment?or rotective factor? that may curtail high-risk behaviors among youth. In other words, among the nearly 100,000 6th to 12th grade students who were surveyed, with consideration for differing family constellations, the more frequently the family had dinner together the less often the adolescent engaged in high-risk behaviors. The high-risk behaviors measured included substance use, sexual activity, depression/suicide, violence, antisocial behaviors, school problems, and binge eating/purging (7). For younger kids ( middle school age) family meals were also a protective factor that supported the development of communication skills and led to greater academic success (8).
Family Meals and Television Watching
Perhaps a less powerful but important aspect of family meals is whether the television is on or off during the meal. The more hours a preschool age child watches television while eating, the greater the liklihood that they will consume more food (9). Children who watched more television and ate fewer family meals were more likely to be overweight by the third grade. (10). The quality of the family dinner appears to be influenced by whether or not the television is turned on. Each night that the family ate dinner together was positively associated with serving fruits or vegetables at the meal. Serving fruits or vegetables decreased with each night the television was on during dinner (11). Teens also reported poorer nutritional intake during family meals that included television watching (12).
However, watching television during family meals was associated with a more healthful diet than not eating regular family meals at all. The biggest factor is not whether the TV is on or off, but whether the family is eating a meal together. Children and teens eat better quality food when they are not alone.
Overall Benefits of Family Meals
Nutrition researchers have long been interested in the family meal and its impact on the health and well-being of children. Eating meals as a family can actually improve children food habits and nutrient intake; parents can model the social behavior they expect; and children and teens will develop social skills and behaviors. We learn our food preferences, our pace of eating, our interaction with others, and our habits of activity at a very young age. Sitting down to dinner with your family will help family members eat a more healthful diet, develop social skills, and possibly avoid high-risk behaviors. In summary, mealtime is important family time. The most important part of family mealtime is simplet the family being together.
Getting Started
It never too early to start having regular family meals, especially since young children want to try what their parents and older siblings eat. Pull the high chair to the table with the rest of the family, even though the infant may only have a few finger foods. Start slowerhaps weekend breakfasts with toddlers might be more relaxed. For preschool children, include foods they like as well as new ones (with you modeling eating and enjoying the ew?food); turn off the TV.
School age children often enjoy helping with the food preparation or setting the table; they like making meals pecial?with candles, place mats, etc; and they can be expected to carry on a conversation. Family meals don have to be elaborate or even have hot foodst being together that counts.
Infants, children and adolescents all depend on regular meals. Regular meals provide the sense to children that their basic needs will be taken care of and that others care about them. Foods offered only when your child asks for something to eat are not considered to be a family meal.
What in some families is called elpy-selfy?is alright as an occasional event, but does not meet emotional, developmental, or nourishment needs when it is a regular practice at the exclusion of family meals.
If you present meals at a more or less regular time and offer a variety of food in a pleasant and matter-of-fact way, your child will grow up to like a range and variety of foods. Your child will also be comfortable and self-assured about choosing appropriate PKU-friendly foods in a variety of social and community settings. Regular family meals and the social interaction they provide are essential for helping your child or adolescent choose to eat the right amount and type of foods to get the body that is right for him or herot too fat, not too thin, but just right and with excellent blood phe levels!
Meal Practices Among PKU Families
On the PKU Listserv, we asked members to tell us about their family meals. Many of you responded with very thoughtful answers and we thank you for sharing with the PKU community. In fact, your responses were so generous that printing all of them would take many more pages than we have available in the newsletter. So we will share some that are representative of the group.
Your responses reflected the ages of your children; whether or not you lived in a rural or urban area, family employment and schedules, and the willingness to include a variety of meal needs into the family meal. This diversity of family situations, while maintaining a commitment to the family meal, we found to be heartwarming.
Making family meals a priority and creating the expectation of regular family meals
More than half of the people who responded reported that the family had an evening meal together six or more times per week; another one third noted they had dinner together 4-5 times/week. Typical responses were:
We try to eat dinner together at home every night during the week. It doesn always happen with school and activities, but it is our goal.
Usually we eat all together as a family at the dinner table since this is the best time we can really be together and go over the days?events.
The only time we don eat together is during sports season because of practice and game times. If one child is absent we still have a family meal. We usually have the TV off for our dinner meal.
We have tried to make family mealtime very important from the beginning. Whether our young son is eating with us or not, we always have him sit in his highchair.
Family Meal Preparation and Encouraging Responsibility
Who prepares the meals at home most often?
Mom won in this category ?hands down.?Most families report that mom plans the meals and prepares most of the food for the entire family. Wonderfully, many families have shared cooking responsibilities, which includes all of the children in the family. Kids have a variety of responsibilities depending on age, skills, and number of children in the family. Typical responses were:
I am responsible for meal planning and preparation; my children help me select some options, such as vegetables, or choosing one of two different meal options. They also set the table and clear their dishes.
Both my husband and I work, so in order to minimize stress I try to plan out the meals ahead of time. Whatever we eat I try to incorporate a similar meal for her as well. For example, if we have spaghetti, then she has spaghetti. I realize she has specific dietary needs but our meals can resemble one another if it is possible.
My son loves to help in the kitchen. I have a few special kid knives purchased from Pampered Chef so he can help with the cutting of veggies/breads, etc. He loves to saut?foods on the stove and helps bake and mix batters for me. He is a super help in the kitchen, even when it comes to cleaning up!
My 16 year-old daughter helps with food preparation. She will peel vegetables, cut up onions, whatever I ask her to do. Also, if I have planned something for my husband and myself that she cannot have, she will prepare something for herself.
My daughter loves to help with dinner. Shel cut veggies for me, like carrots or celery. If we have mashed potatoes, she gets to do the mashing. When we have grilled cheese and tomato soup, she is always in charge of the sandwiches. Her grilled cheese consists of a slice of low pro bread, buttered on both sides and grilled. She also makes the regular grilled cheese. If I not home to make dinner she will generally make her own. She usually makes pasta or rice, soup and sandwiches.
How Do PKU Families Manage Eating Out?
Again, family practice depends on age of child or children, family resources, and location. Some families eat out very seldom; about 40% of families reported that they eat out frequentlyt least once or twice a week; and another one-third noted that they eat out from once to three times per month.
Typical responses were from families who have developed innovative ways to include all family members in a o fuss?manner.
We usually eat out together about 1 or 2 times a week and we try to make Sunday dinner a tradition at Grammy house.
We usually go out to eat once or twice each week. We try to either go someplace that has items my son can eat or else we take special items for him to eat.
We eat out approximately 3 times a month. With my son being older, he usually orders the buffet so he can get the salad and a baked potato.
We eat ake-out?or in a restaurant about 2-4 times/month and have found which restaurants have microwaves and have learned which have PKU-friendly menus.
Summary of PKU Family Responses
In the PKU community, the family meal seems to be live and well,? at least among families who responded to our questionaire. Families and their children are flexible and creative in providing a healthy and supportive family environment for all of their children.
Based on the research reviewed here and the testimony of listserv members, there are many ways to achieve family togetherness and a healthy family meal. Family togetherness and family role modeling appears to be a more powerful motivation for the family meal than the food. The habits of eating together developed in childhood will continue to support good health into adulthood.
Parents?Most Important Role
From the very beginning, parents and family members model important roles for children. The adults in a child life model what to do, what not to do, and how to handle daily life. This modeling plays a very important role in a child growth and development and sets the tone for children behavior. If a parent is a positive role model for healthy food choices, regular meals, and physical activity habits, children are more willing and more likely to do the same.
As a parent it is often easier to promote the axiom o as I say?instead of o as I do.? Parents whose children have PKU may find themselves drawn to an authoritative approach to food and eating because of the prescribed parameters of food and medical food intake. This type of authoritative parenting can work against successful nourishment and parenting interactions around food choices. Many children will see the emand?that a certain food be eaten at a certain time as a urf atter and many will rebel and refuse the food. On the other hand, modeling positive behaviors teaches children about appropriate foods choices, and appropriate portion sizes of foods without the authoritative approach. It also emphasizes shared responsibility for nourishment and behavior; that is, everyone in the family has a role in the family meal (for example, food preparation, choosing the amount of food to eat, clearing the dishes from the table).
The PKU families in our survey noted that positive strategies for meals in their family included: offering food with a positive, but neutral tone; offering a choice of fruits and vegetables for all family members at meals; assuring that each family member had appropriate ilk?to drink at each meal; having a regular rotation among family members in choosing the vegetable or, perhaps, the dessert for the meal; and assuring that each person in the family had an age and skill appropriate role in the meal preparation and clean-up. Children who are actively involved with their families in any aspect of the family meal have a head start on developing self-confidence in social situations outside of the immediate family.
Resources
A valuable resource for families and health care professionals alike is the Bright Futures series of materials at www.brightfutures.aap.org (American Academy of Pediatrics). Bright Futures: Guidelines for Health Supervision of Infants, Children, and Adolescents was developed to provide comprehensive health supervision and parent guidelines with detailed anticipatory guidance for ages and stages of development. Bright Futures provides guidelines that focus on physical activity, nourishment, and health behaviors for each age and stage.
Another important resource is Ellyn Satter (www.ellynsatter.com), a nutritionist who has researched and taught about the importance of family meals for decades. She provides some essential concepts that apply to all family members, regardless of health status. A monthly newsletter (Family Meals Focus) and well-researched guidelines are provided at www.ellynsatter.com/newsletter.htm.
References
1. Hong D. The Happiest Meal of All. Seattle Times, Nov 24, 2006.
2. Rockett HRH. Family Dinner: More Than Just a Meal. J Amer Diet Assoc. 107: 1498-1501, 2007.
3. Schnurnberger L. The Truth about Family Meals. Parade Magazine Nov 11, pages 10-11, 2007.
4. Larson NI et al. Family meals during Adolescence are Associated with Higher Diet Quality and Healthful Meal Patterns during Adulthood. J Amer Diet Assoc. 107: 1502-1510, 2007.
5. Boutelle KN et al. Fast food family meals: relationships with patent and adolescent food intake, home food availability and weight status. Public Health Nutr 10: 16-23, 2007.
6. Fulkerson JA et al. Adolescent and parent views of family meals. J Amer Diet Assoc 106: 526-532, 2006.
7. Fulkerson JA et al. Family dinner meal frequency and adolescent development: relationships with developmental assets and high-risk behaviors. J Adolesc Health 39: 337-345, 2006.
8. Gillman MW et al. Family dinner and diet quality among older children and adolescents. Arch Family Med 9: 235-240, 2000.
9. Francis L et al. Does Eating during television Viewing Affect Preschool Children Intake? J Amer Diet Assoc 106: 598-600, 2006.
10. Gable S et al. Television Watching and Frequency of Family Meals are Predictive of Overweight Onset and Persistence in a National Sample of School-Aged Children. J Amer Diet Assoc. 107: 53-61, 2007.
11.Fitzpatrick E et al. Positive effects of family dinner are Undone
Some have expressed concerns about the safety of aspartame, and there has been debate over whether it might be linked to a variety of symptoms and illnesses. However, based on current scientific evidence, the U.S. Food and Drug Administration (FDA) has approved aspartame as safe for kids and adults to consume. (The FDA has also approved four other artificial sweeteners: saccharine, acesulfame potassium [acesulfame-K], neotame, and sucralose.)
Government regulators in more than 100 other countries, along with independent groups such as the American Medical Association (AMA) and the World Health Organization (WHO), also have said that food and drinks containing aspartame are safe as long as they're part of a balanced diet.
The FDA does recommend that kids and adults limit how much aspartame they consume to no more than 50 milligrams of aspartame per 2.2 pound (1 kilogram) of body weight per day. The average person consumes less that 2% of this amount per day, so it would be difficult to consume harmful amounts of aspartame.
Here's a quick guide to popular products and the average amount of aspartame in each serving:
12 ounces (360 milliliters) of diet soda = 225 milligrams of aspartame
½ cup (120 milliliters) of sugar-free frozen dairy dessert (frozen yogurt, ice cream, etc.) = 47 milligrams of aspartame
1 packet of artificial sweetener = 37 milligrams of aspartame
Some people should avoid aspartame. Anyone who has the rare hereditary disease phenylketonuria (PKU) is unable to break down the compound phenylalanine, which is in aspartame. Consumption of too much aspartame can result in brain damage and cognitive impairment for anyone with PKU.
The FDA requires all products that contain artificial sweeteners to state that on the label. However, if you are concerned about your kids' aspartame consumption, talk with your doctor.
There are a number of lower phe substitutes for high protein foods. (For example,
low phe peanut butter, imitation cheese, cream cheese, and cheese sauces, and
imitation chocolate are available.) These foods are generally lower in phe than their
look-alikes, but are not free foods. Here are some things to consider when deciding
whether or not these products are right for your child with PKU. You can use these
questions to decide your approach to other “sometimes” foods too.
1. Does your child clearly understand the difference between high protein foods
and look-alike foods?
2. How BIG is your child’s appetite?
• Will he or she be satisfied with “just a little”?
• Would it be easier to have “yes” foods that could be eaten in (nearly)
unlimited amounts to satisfy his or her appetite?
3. What is your child’s “phe tolerance”?
• Is there room in your child’s food pattern to incorporate additional phe from
non-essential foods?
• What other foods are you willing to limit to include the look-alike foods?
4. Is the look-alike product acceptable? Is it readily available?
• What is the cost of the food substitute?
• Is the product acceptable with regards to appearance, taste, texture?
5. How will the look-alike food be used?
• If it will be used as a treat, will your child think that low phe foods are “not
as good” as high phe foods or look-alike foods?
• Will the look-alike food encourage/support compliance with regular use?
• Will it become another issue of “negotiation”?
What is Included in a Low Phenylalanine Food Pattern?
The diet for PKU consists of a phenylalanine-free medical formula and carefully measured amounts of fruits, vegetables, bread, pasta, and cereals. Many people who follow a low phenylalanine (phe) food pattern eat special low protein breads and pastas. They are nearly free of phe, allow greater freedom in food choices, and provide energy and variety in the food pattern.
What is Not Included in a Low Phenylalanine Food Pattern?
Foods that contain large amounts of phe must be eliminated from a low phe diet. These foods are high protein foods, such as milk, dairy products, meat, fish, chicken, eggs, beans, and nuts. These foods cause high blood phe levels for people with PKU.
Aim for Healthy Choices
This target is an easy way to visualize the foods allowed on the diet for PKU. The phenylalanine-free formula, such as Phenyl-Free*, is the center of the target diet. As the foods get further away from the bull's-eye, they are higher in phenylalanine. The foods outside the target are not included in the low-phenylalanine meal plan.
How Can This Food Pattern be Enough?
It is not unusual for someone who follows a low phe diet to have 2 kinds of vegetables and a baked potato for dinner. However, if these foods were the only foods a person consumed, his or her diet would be lacking protein, vitamins, and minerals. That is where the special formula comes in.
A special phenylalanine-free formula, such as Phenyl-Free*, contains protein, vitamins, minerals and energy (calories) with no phenylalanine. With formula, a person with PKU gets plenty of protein, without the side effects of the high phe content of most foods. The phenylalanine-free formula is the most important part of the diet for PKU.
How Long Must a Person With PKU Follow This Special Diet?
Research has shown that this diet should be followed for life. Keeping blood phe levels in the safe range helps to prevent problems with thinking and problem solving.
In the past, people with PKU were advised to stop their low phe diet when they were children. Most young people with PKU who were taken "off diet" did not monitor their blood phe levels and were not given any reason to be concerned about them. These people began to experience problems with paying attention, concentrating, and remembering. Recently, many of these same people have decided to go back "on diet" hoping to feel better. In order to go "on diet" a person must drink a special phenylalanine-free formula and choose low phe foods so that blood phe levels are in the safe range.
It is never too late to go back "on diet." A low phe diet helps most young adults with PKU to feel better and improves attention span, concentration, and memory. In general, young adults who have made these changes report that they think and feel better. The effort that it takes to bring down blood phe levels is well worth it for everyone, no matter how long they have been "off diet."
* Phenyl-Free is a registered trademark of Mead Johnson Co. A number of other formulas are available.
Journal Articles
What is phenylketonuria?
Phenylketonuria (commonly known as PKU) is an inherited disorder that increases the amount of the amino acid phenylalanine to harmful levels in the blood. (Amino acids are the building blocks of proteins.) If PKU is not treated, excess phenylalanine can cause mental retardation and other serious health problems.
Phenylketonuria is a subtype of hyperphenylalaninemia.
The signs and symptoms of this disorder vary from mild to very severe. The most severe form of the disorder is known as classic PKU. Infants with classic PKU appear normal until they are a few months old. Without treatment, these children develop permanent mental retardation and behavioral problems. Seizures, delayed development, and movement disorders are also common. Many children have a musty or "mouse-like" odor as a side effect of too much phenylalanine in the body. Children with classic PKU tend to have lighter skin and hair than unaffected family members, because phenylalanine is important for skin pigmentation. Children with the disorder are also likely to have skin disorders such as eczema.
Less severe forms of PKU (sometimes called moderate or mild PKU) have a smaller risk of brain damage. People with very mild cases may not require treatment with a special diet.
Babies born to mothers with high levels of phenylalanine have a high risk of mental retardation because they are exposed to very high levels of phenylalanine before birth. These infants may also grow more slowly than other children and may have heart defects or other heart problems, small head size (microcephaly), and behavioral problems. Affected women with uncontrolled phenylalanine levels also have an increased risk of pregnancy loss.
How common is phenylketonuria?
PKU is found in about 1 in 10,000 Caucasian (white) newborns. The disorder occurs much less frequently in infants of Japanese, Ashkenazi Jewish, Finnish, and African backgrounds. PKU is most common in Turkey, where 1 in 2,600 newborns is affected.
What genes are related to phenylketonuria?
Mutations in the PAH gene cause phenylketonuria.
PAH produces an enzyme called phenylalanine hydroxylase, which converts the amino acid phenylalanine to other essential compounds in the body. Normal levels of phenylalanine are important for brain function. This amino acid is found in all proteins and in some artificial sweeteners. If gene mutations reduce the activity of phenylalanine hydroxylase, phenylalanine from the diet can build up to dangerous levels in the bloodstream and other tissues. Excess phenylalanine damages nerve cells, resulting in brain damage.
How do people inherit phenylketonuria?
PKU is inherited in an autosomal recessive pattern, which means two copies of the gene must be altered for a person to be affected by the disorder. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene.
What other names do people use for phenylketonuria?
Classical Phenylketonuria
Deficiency Disease, Phenylalanine Hydroxylase
Folling Disease
Phenylalanine Hydroxylase Deficiency Disease
Phenylketonuria I
PKU
Source: Genetics Home Reference, National Library of Medicine, National Institutes of Health
Phenylketonuria
Phenylketonuria (PKU) is an inherited error of metabolism caused by a deficiency in the enzyme phenylalanine hydroxylase. Loss of this enzyme results in mental retardation, organ damage, unusual posture and can, in cases of maternal PKU, severely compromise pregnancy.
Classical PKU is an autosomal recessive disorder, caused by mutations in both alleles of the gene for phenylalanine hydroxylase (PAH), found on chromosome 12. In the body, phenylalanine hydroxylase converts the amino acid phenylalanine to tyrosine, another amino acid. Mutations in both copies of the gene for PAH means that the enzyme is inactive or is less efficient, and the concentration of phenylalanine in the body can build up to toxic levels. In some cases, mutations in PAH will result in a phenotypically mild form of PKU called hyperphenylalanemia. Both diseases are the result of a variety of mutations in the PAH locus; in those cases where a patient is heterozygous for two mutations of PAH (ie each copy of the gene has a different mutation), the milder mutation will predominate.
A form of PKU has been discovered in mice, and these model organisms are helping us to better understand the disease, and find treatments against it. With careful dietary supervision, children born with PKU can lead normal lives, and mothers who have the disease can produce healthy children.
What is phenylketonuria (PKU)?
Phenylalanine is an essential amino acid, which means the body must have it to grow and function properly. Too much can be harmful, so the body uses the enzyme phenylalanine hydroxylase to convert it into tyrosine.
In PKU, levels of this enzyme are low. This means only limited amounts if phenylalanine can be converted into tyrosine. As a result, phenylalanine build ups in the blood and other body tissues, particularly the brain, where it can cause severe and irreversible damage.
Symptoms
If PKU isn't detected early, progressive developmental delay and severe learning difficulties can occur. Other problems may include epilepsy and eczema.
Children with PKU typically have very fair hair and their urine has a musty smell.
PKU affects about one in 10,000 people. Classic PKU and several less common variants are all inherited in an autosomal recessive fashion, meaning that if both parents are carriers, each child has a 1 in 4 chance of having the disease. The PKU gene is found on chromosome 12.
All newborn babies are screened for PKU using a heel-prick blood sample. Antenatal screening is also available
Treatment and recovery
There's no cure for PKU but starting a low-phenylalanine diet as soon as possible after birth can help to avoid the harmful effects.
Phenylalanine is found in many proteins, so protein-rich foods such as meat must be avoided and replaced with 'safe' proteins, usually in the form of specially formulated substitutes. This diet should be followed in the long term.
Women with PKU must follow this diet while pregnant or they risk exposing their unborn children to high levels of the amino acid. This can lead to miscarriage, birth defects and brain damage, even if the children don't inherit PKU themselves.
Definition
Phenylketonuria (fen-ul-ke-to-NU-re-uh) is a birth defect in which a mutation occurs in a gene containing instructions for making the enzyme needed to break down the amino acid phenylalanine.
Amino acids are the building blocks for protein, and too much phenylalanine can cause a variety of health problems. People with phenylketonuria — babies, children and adults — need to follow a diet that limits phenylalanine, which is found mostly in high-protein foods.
Babies in the United States and many other countries are screened for phenylketonuria soon after birth. Although phenylketonuria is rare, recognizing phenylketonuria right away can help prevent serious health problems.
Phenylketonuria (commonly known as PKU) is an inherited disorder that increases the amount of the amino acid phenylalanine to harmful levels in the blood. (Amino acids are the building blocks of proteins.) If PKU is not treated, excess phenylalanine can cause mental retardation and other serious health problems.
Phenylketonuria is a subtype of hyperphenylalaninemia.
The signs and symptoms of this disorder vary from mild to very severe. The most severe form of the disorder is known as classic PKU. Infants with classic PKU appear normal until they are a few months old. Without treatment, these children develop permanent mental retardation and behavioral problems. Seizures, delayed development, and movement disorders are also common. Many children have a musty or "mouse-like" odor as a side effect of too much phenylalanine in the body. Children with classic PKU tend to have lighter skin and hair than unaffected family members, because phenylalanine is important for skin pigmentation. Children with the disorder are also likely to have skin disorders such as eczema.
Less severe forms of PKU (sometimes called moderate or mild PKU) have a smaller risk of brain damage. People with very mild cases may not require treatment with a special diet.
Babies born to mothers with high levels of phenylalanine have a high risk of mental retardation because they are exposed to very high levels of phenylalanine before birth. These infants may also grow more slowly than other children and may have heart defects or other heart problems, small head size (microcephaly), and behavioral problems. Affected women with uncontrolled phenylalanine levels also have an increased risk of pregnancy loss.
How common is phenylketonuria?
PKU is found in about 1 in 10,000 Caucasian (white) newborns. The disorder occurs much less frequently in infants of Japanese, Ashkenazi Jewish, Finnish, and African backgrounds. PKU is most common in Turkey, where 1 in 2,600 newborns is affected.
What genes are related to phenylketonuria?
Mutations in the PAH gene cause phenylketonuria.
PAH produces an enzyme called phenylalanine hydroxylase, which converts the amino acid phenylalanine to other essential compounds in the body. Normal levels of phenylalanine are important for brain function. This amino acid is found in all proteins and in some artificial sweeteners. If gene mutations reduce the activity of phenylalanine hydroxylase, phenylalanine from the diet can build up to dangerous levels in the bloodstream and other tissues. Excess phenylalanine damages nerve cells, resulting in brain damage.
How do people inherit phenylketonuria?
PKU is inherited in an autosomal recessive pattern, which means two copies of the gene must be altered for a person to be affected by the disorder. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene.
What other names do people use for phenylketonuria?
Classical Phenylketonuria
Deficiency Disease, Phenylalanine Hydroxylase
Folling Disease
Phenylalanine Hydroxylase Deficiency Disease
Phenylketonuria I
PKU
Source: Genetics Home Reference, National Library of Medicine, National Institutes of Health
Phenylketonuria
Phenylketonuria (PKU) is an inherited error of metabolism caused by a deficiency in the enzyme phenylalanine hydroxylase. Loss of this enzyme results in mental retardation, organ damage, unusual posture and can, in cases of maternal PKU, severely compromise pregnancy.
Classical PKU is an autosomal recessive disorder, caused by mutations in both alleles of the gene for phenylalanine hydroxylase (PAH), found on chromosome 12. In the body, phenylalanine hydroxylase converts the amino acid phenylalanine to tyrosine, another amino acid. Mutations in both copies of the gene for PAH means that the enzyme is inactive or is less efficient, and the concentration of phenylalanine in the body can build up to toxic levels. In some cases, mutations in PAH will result in a phenotypically mild form of PKU called hyperphenylalanemia. Both diseases are the result of a variety of mutations in the PAH locus; in those cases where a patient is heterozygous for two mutations of PAH (ie each copy of the gene has a different mutation), the milder mutation will predominate.
A form of PKU has been discovered in mice, and these model organisms are helping us to better understand the disease, and find treatments against it. With careful dietary supervision, children born with PKU can lead normal lives, and mothers who have the disease can produce healthy children.
What is phenylketonuria (PKU)?
Phenylalanine is an essential amino acid, which means the body must have it to grow and function properly. Too much can be harmful, so the body uses the enzyme phenylalanine hydroxylase to convert it into tyrosine.
In PKU, levels of this enzyme are low. This means only limited amounts if phenylalanine can be converted into tyrosine. As a result, phenylalanine build ups in the blood and other body tissues, particularly the brain, where it can cause severe and irreversible damage.
Symptoms
If PKU isn't detected early, progressive developmental delay and severe learning difficulties can occur. Other problems may include epilepsy and eczema.
Children with PKU typically have very fair hair and their urine has a musty smell.
PKU affects about one in 10,000 people. Classic PKU and several less common variants are all inherited in an autosomal recessive fashion, meaning that if both parents are carriers, each child has a 1 in 4 chance of having the disease. The PKU gene is found on chromosome 12.
All newborn babies are screened for PKU using a heel-prick blood sample. Antenatal screening is also available
Treatment and recovery
There's no cure for PKU but starting a low-phenylalanine diet as soon as possible after birth can help to avoid the harmful effects.
Phenylalanine is found in many proteins, so protein-rich foods such as meat must be avoided and replaced with 'safe' proteins, usually in the form of specially formulated substitutes. This diet should be followed in the long term.
Women with PKU must follow this diet while pregnant or they risk exposing their unborn children to high levels of the amino acid. This can lead to miscarriage, birth defects and brain damage, even if the children don't inherit PKU themselves.
Definition
Phenylketonuria (fen-ul-ke-to-NU-re-uh) is a birth defect in which a mutation occurs in a gene containing instructions for making the enzyme needed to break down the amino acid phenylalanine.
Amino acids are the building blocks for protein, and too much phenylalanine can cause a variety of health problems. People with phenylketonuria — babies, children and adults — need to follow a diet that limits phenylalanine, which is found mostly in high-protein foods.
Babies in the United States and many other countries are screened for phenylketonuria soon after birth. Although phenylketonuria is rare, recognizing phenylketonuria right away can help prevent serious health problems.
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