Phenylketonuria (PKU) is a disorder of amino acid metabolism, which causes a clinical syndrome characterized by mental retardation, cognitive and behavioral disorders due to elevated serum phenylalanine. The primary cause is an inactivity of the phenylalanine hydroxylase. The diagnosis is made by high phenylalanine and tyrosine levels normal or low. The therapy is a lifelong Phenylalaninrestriktion. The prognosis is excellent with treatment.
Phenylketonuria are frequently found in the Caucasian population, it is less common among Ashkenazi Jews, the Chinese and African American population. The inheritance is autosomal recessive, the incidence is in Caucasians about 1 / 10,000 live births.
Phenylketonuria (PKU) is a disorder of amino acid metabolism, which causes a clinical syndrome characterized by mental retardation, cognitive and behavioral disorders due to elevated serum phenylalanine. The primary cause is an inactivity of the phenylalanine hydroxylase. The diagnosis is made by high phenylalanine and tyrosine levels normal or low. The therapy is a lifelong Phenylalaninrestriktion. The prognosis is excellent with treatment. Phenylketonuria are frequently found in the Caucasian population, it is less common among Ashkenazi Jews, the Chinese and African American population. The inheritance is autosomal recessive, the incidence is in Caucasians about 1 / 10,000 live births. For information on other related diseases amino acid phenylalanine and tyrosine see Table metabolic disorders. See also approach in a patient with suspected congenital metabolic disorder pathophysiology tetrahydrobiopterin (BH4) is an essential cofactor for this reaction. Excess phenylalanine (z. B. which is not used for protein synthesis) is normally ungewandelt by the phenylalanine to tyrosine. Due to a possible malfunction of the brain myelination of which is mainly affected. If one of the many gene mutations leading to deficiency or absence of phenylalanine hydroxylase, is orally ingested phenylalanine accumulates. Another part of the excess phenylalanine is metabolized to phenyl ketones, which are excreted in urine and have led to the name phenylketonuria. The extent of enzyme defect, and therefore, the severity of hyperphenylalaninemia varies depending on the particular mutation. Variable forms Although almost all cases (98-99%) of PKU result from a lack of phenylalanine hydroxylase, phenylalanine can also accumulate when BH4 is not synthesized due to a lack of Dihydrobiopterinsynthese or not regenerated due to lack of dihydropteridine. In addition, the BH4 deficiency causes a change in the synthesis of the neurotransmitter, as it is involved in the synthesis of dopamine and serotonin. So neurological symptoms may occur independently of a phenylalanine accumulation. Symptoms and signs Most children with phenylketonuria are normal at birth and develop slowly, when the phenylalanine accumulates over several months, the symptoms and findings. The main feature of PKU is a mental disability. The children also exhibit exceptional hyperactivity, gait disorders, psychosis and an unpleasant, mouse-like body odor which (a degradation product of phenylalanine) is caused in the urine and sweat by phenylacetate. The children tend to have lighter skin, lighter hair and lighter eye color, as non-affected family members, and some may have a rash – like a child’s eczema – develop. Diagnosis Routine newborn screening phenylalanine levels in the United States and many developed countries are examined all newborns, 24-48 h after birth with one of many blood tests for phenylketonuria; pathological results are confirmed with a direct determination of phenylalanine. In classical PKU newborns often phenylalanine> 20 mg / dl (1.2 mmol / l) have. Patients with a partial deficiency have levels <8-10 mg / dl when they eat normal (mirror> 6 mg / dl are treatment charge). Differentiation from a classic PKU sometimes makes a liver phenylalanine hydroxylase activity assay necessary to measure an activity of between 5% and 15% of the normal value or a mutation analysis to identify slight mutations in the gene. BH4 deficiency is distinguished from other forms of PKU by increased concentrations of biopterin and neopterin in urine, blood, cerebrospinal fluid, or all three. The identification is important, and the urinary biopterin profile should be routinely determined at initial diagnosis, since a PKU-standard treatment in this case can not prevent neurological damage. Children from families with a positive family history should be prenatally diagnosed through direct mutation studies after a chorionic villus sampling or amniocentesis. Forecast prevents Adequate treatment on the first day of life all manifestations of this disease. If treatment is started only after 2-3 years, only the hyperactivity and intractable seizures can be controlled. Children of mothers with poorly controlled PKU (z. B. with a high phenylalanine) have to develop a high risk of microcephaly or developmental retardation during pregnancy. Therapy restriction of phenylalanine in the diet therapy of phenylketonuria is a lifelong Phenylalaninrestriktion. All natural proteins contain about 4% phenylalanine. Therefore, the dietary recommendations foods contain a low protein content (eg. As fruits, vegetables and some grain types) treated protein hydrolysates, remove the phenylalanine and phenylalanine-free amino acid mixtures. Examples of commercially available phenylalanine-free foods are Phe-products (PKU Anamix® for infants, XP Maxamaid® for children between 1 and 8 years, XP Maxamum® for children> 8 years), Phenex® 1 and Phenex®-2, phenyl -Free® 1 and phenyl-Free® 2, PKU 1, 2 and PKU PKU 3, PhenylAde® (variations), PKU Loflex LQ® and Plexy-10® (multiple formations). The body needs small amounts of phenylalanine for growth and metabolism, which are provided by measured amounts of milk or low-protein foods. The Phenylanalinspiegel in the blood must be inspected frequently. The recommended standard values ??are between 2 mg / dl and 4 mg / dl (120-240 mol / l) <12 years and between 2 mg / dL and 10 mg / dl (120 to 600 mol / l) for children children> 12 years. In women of childbearing age the diet plan must be started before pregnancy to allow the child optimal development. The tyrosine supplementation is increasingly used because it is an essential amino acid in patients with PKU. In addition, more and more often sapropterin is used. For children with BH4 deficiency, the treatment additionally comprises tetrahydrobiopterin, 1-5 mg / kg p.o. 3 times a day and levodopa, carbidopa and 5-OH-tryptophan and folic acid 10-20 mg p.o. once a day in case of dihydropteridine deficiency. The goals of treatment are the same as in PKU. Important points PGU is triggered by one of several genetic mutations that lead to a deficiency or absence of phenylalanine hydroxylase, so that orally ingested phenylalanine accumulates. Due to a possible malfunction of the brain myelination of which is mainly affected. PKU causes a clinical syndrome characterized by mental retardation, cognitive and behavioral disorders; untreated done a severe mental disability. In the US and many developed countries all newborns are 24-48 h after birth with a studied by many blood tests for phenylketonuria; pathological results are confirmed with a direct determination of phenylalanine. The treatment consists in a lifelong restriction of phenylalanine; adequate treatment on the first day of life prevents all manifestations of this disease. Although the prognosis for treatment is excellent, the Phenylanalinspiegel in the blood must be inspected frequently. The recommended standard values ??are between 2 mg / dl and 4 mg / dl (120-240 mol / l) <12 years and between 2 mg / dL and 10 mg / dl (120 to 600 mol / l) for children children> 12 years.