Phenylketonuria

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.