Phenylketonuria

Phenylketonuria is one of the most significant causes of dietary preventable mental retardation. As a result of a partial or complete deficiency of the enzyme phenylalanine hydroxylase (PAH), which is involved in the conversion of the amino acid phenylalanine to tyrosine, the plasma level of phenylalanine is increased above the normal level. An elevated level of phenylalanine causes neurotoxicity through various mechanisms (neurotransmitter deficiency, oxidative stress, decreased protein synthesis). Phenylketonuria is inherited in an autosomal recessive manner. The global prevalence of phenylketonuria is estimated to be 1:23930 live births. Studies conducted in Turkey have shown that the prevalence of hyperphenylalaninemia is 1:2785 and the prevalence of phenylketonuria is 1:4370. The most common cause of PAH deficiency is PAH gene mutations. Less common causes of hyperphenylalaninemia include disorders of BH4 metabolism, DNAJC12 deficiency and transient tyrosinemia of the newborn. In classical phenylketonuria, a diet therapy that restricts phenylalanine intake is highly effective when initiated early. Animal protein sources with a particularly high protein value are excluded from the diet. When blood phenyl alanine levels are kept within the target range (<360 µmol/L under 12 years of age, <600 µmol/L above 12 years of age), patients can complete their neuromotor development similar to their peers. Therefore, newborn screening programmes are very important for the early detection of patients with classical phenylketonuria.