HYPERPHENYLALANINEMIA: CASE REPORT

Abstract

Background: Hyperphenylalaninemia (HPA) is a group of autosomal recessive diseases caused by impaired metabolism of the essential amino acid phenylalanine (Phe), which enters the human body with protein food [1]. HFA combines several genetically heterogeneous forms of phenylalanine metabolism disorders similar in clinical features: classical phenylketonuria (PKU), caused by phenylalanine-4-hydroxylase (PAH) deficiency and hyperphenylalaninemia (HPA), associated with tetrahydrobiopterin (BH4) metabolic disorders [2]. The pterin-dependent form of hyperphenylalaninemia accounts for about 2% of all cases of HPA. These conditions are caused by a deficiency of enzymes involved in the synthesis or reduction of tetrahydrobiopterin (BH4), which is a PAH cofactor, as well as tyrosine hydroxylase and tryptophan hydroxylase [3, 4]. Currently, several genetically heterogeneous forms of BH4-deficient HPA are known: type A, 6-pyruvoyltetrahydropterine synthase (PTPS) deficiency, type B, guanosine triphosphate cyclohydrolase 1 (GTPCH) deficiency, type C, dihydropterine reductase (DHPR) deficiency, type D, pterin-4a-α-carbinolamine dehydratase (PCBD) deficiency, DOPA-dependent dystonia caused by sepiapterin reductase (SPR) deficiency and HPA without tetrahydrobiopterin deficiency, caused by mutations in the DNAJC12 gene encoding the JDP1 protein [5, 6]. Pterin-dependent forms of HPA have clinical manifestations similar to classical PKU. In these forms, the main role in the pathogenesis is played by a severe deficiency in the neurotransmitters of the catecholamine and serotonin series, which makes isolated diet therapy meaningless and requires different approaches to treatment. The complex of treatment for such patients includes BH4 or its synthetic analogs [3-5].