Phenylketonuria,PKU

Etiology:High amphetamine acidosis (Hyperphenylalaninemia), also known as PKU (phenylketonuria), is an autosomal recessive genetic disease, mainly due to the body phenylalanine (phenylalanine; Phe) hydroxylation (hydroxylation) into tyrosine (tyrosine ; Tyr) metabolic pathways of local failure caused by congenital metabolic disorders. There are five different enzymes are known to be the cause of such a lack of metabolic barrier according to their lack of different machines, different clinical symptoms and diagnosis, the treatment methods are not the same.
Five different enzymesPhenylalanine hydroxylase enzyme Phenylalanine hydroxylase / PAH PAH deficiencyGuanine nucleoside triphosphate hydrolase cyclization Gtp cyclohydrolase I / GTPCHI BH4 deficiencyPropanedione tetrahydro neopterin synthesis enzyme 6-pyruvoyl tetrahydropterin synthase / PTPS BH4 deficiencyHydrochlorothiazide pteridine reductase dihydropteridine reductase / DHPR BH4 deficiencyNeopterin methanolamine dehydrated enzyme pterin-4-carbinolamine dehydratase / PCD BH4 deficiencyIncidence:Europe and the United States occur in approximately ten thousandth, eight hundred and seventy thousand domestic newborn screening results show that the incidence is about 1/34000.
Genetic model:Is an autosomal recessive genetic disease, the parents each with a mutated gene, but no clinical symptoms were due to be called with. Patients themselves must be the same time with two mutant genes (by the parents each get a mutated gene) before onset; as long as both parents are carriers, then each tire gender birth disease probability is 1/4 .
Clinical features:Patients because they can not metabolize food protein contains phenylalanine, resulting in the accumulation of phenylalanine in the blood, and thus the infant or child's brain and central nervous system, causing permanent damage, resulting in mental retardation. If diagnosed early, giving last a lifetime diet, can effectively prevent mental retardation issue. According to foreign reports in the literature of patients treated within one month, the average IQ of 95, one to two months before the treatment of the patients, with an average IQ of 85; rather late treated or untreated, their average IQ of 53-45 . The first enzyme phenylalanine hydroxylase (PAH) deficiency: The most common cause typical phenylketonuriaShow clinical symptoms of yellow hair, pale skin dryness and intelligent disability sequelae. PKU patients in Europe and America about 98 ~ 99% for this type of domestic PKU patients only about 70 to 80% of patients with this type.The second to the fifth cause lack of phenylalanine into tyrosine hydroxylase coenzyme necessary when methotrexate tetrahydro Health (tetrahydrobiopterin; BH4) deficiencyThe clinical symptoms in addition to some of the typical symptoms of phenylketonuria, there are strict kind of neurological symptoms (such as convulsions), growth retardation, easy to infection. China's PKU patients about 20% to 30% of the students neopterin tetrahydro-deficient, the special needs of the differential diagnosis in order to take proper treatment.
Diagnosis:Newborn screening filter paper blood spots were measured specimen phenylalanine levels, when the concentration is higher than 120 mM blood should further review, phenylalanine concentrations continue to rise if the phenomenon, which should be recognized and differential diagnosis. Also screening in the neonatal period such amino acid metabolism, the need to pay attention to whether the case has been getting enough protein (feeding more than 48 hours), in order to avoid the generation of false negatives.Positive cases may be due to liver dysfunction caused by a temporary increase in the concentration of phenylalanine, or because of congenital metabolic enzyme phenylalanine deficiency leads to high amphetamine acidosis (Hyperphenylalaninemia), thus further confirm the diagnosis. Confirm the diagnosis in addition to the clinical assessment of pediatric specialist outside laboratory confirmation method for the analysis of blood and urine related to the content of amino acids, and the need to tie in with other related analysis to confirm the diagnosis.Distinguish between patients with PAH deficiency or lack of BH4 methods include oral BH4 loading test (BH4 loading test), neopterin urine (urine pterin) analysis neurotransmitters cerebrospinal fluid (CSF neurotransmitter) analysis, quantification of erythrocyte DHPR activity. Oral BH4 loading test was monitored after oral BH4 concentration of phenylalanine in the blood is decreased, and if more than 30% decline, it means taking the case on BH4 responsive (responsive), may consider the use of oral BH4 treatment. However, this test need blood once every two hours, so be patient way to detect better.
Treatment:Without early treatment will result in severe mental retardation, so the damage to the brain disease is progressive in nature, and therefore more asymptomatic newborn babies, about 3 to 4 months or so symptoms will slowly appear. The sooner the better therapeutic effect, according to foreign reports in the literature that patients treated within a month, the average IQ of 95,1 ~ 2 months before treatment of patients with an average IQ of 85; while receiving treatment or therapy of advanced , their average IQ of 53-45. PAH-deficient patients in the neonatal period begins when a good diet, then IQ is different from normal people, and the growth is completely unaffected. BH4-deficient patients also suggested to be added in the neonatal period began to accept the treatment of central nervous conduction precursor substances.Patients received dietary or drug treatment, requiring regular ISR growth and development, intellectual development, blood and other essential amino acids phenylalanine concentration to confirm whether diet or medication appropriate. If caught and treated early, you can avoid the complications of mental retardation.

PAH deficiency / classic phenylketonuria (food type)Treatment depends mainly on diet control, and strictly limit the intake of phenylalanine, therefore need under the direction of a physician or nutritionist, eating a small amount of baby milk formula or a general after the age of a low-protein diet, and with a special formula milk (milk without phenylalanine ) replenish amino acids necessary to maintain normal growth and physiological functions.
Need to last a lifetime diet, female patients of childbearing age should be more strictly controlled to avoid maternal phenylketonuria (maternal PKU), resulting in the generation born disabled children produce. Some cases can be helped by medication, a slight relaxation diet, has reached more humane treatment goals and better prognosis.
BH4 deficiency (medication type)Treatment includes giving BH4 (1-5 mg / kg / day), may need to be controlled with diet has achieved the desired concentration of phenylalanine in the blood and central nervous conduction pioneer supplementary substances, including L-dopa and 5-hydroxy tryptophan. For DHPR deficient patients required additional supplementary Folinic acid.

Prognosis:Precautions everyday lifeIf the value of the U.S. youth revolt of the patient, often different from many people wanting his peers, so give diet therapy and companions started eating the same food, the cause of many behavioral deviations, even if during this period some patients pregnancy, will produce very serious deformity children.So we need to help these suffering children, to understand and to give them timely encouragement and support to assist them survive; Because patients can eat extremely limited, and special milk tastes really hard to swallow. This disease has now developed a number of low-phenylalanine foods for patients with this disease, but few domestic manufacturers are willing to import these foods, because the patient is small and low profits, while the vast majority of families also can not afford these expensive costs, hope that these patients can take control of their diet, it is a bit reluctant.