HYPERPHENYLALANINEMIA DUE TO TETRAHYDROBIOPTERIN DEFICIENCY - A REPORT OF 16 CASES

Tetrahydrobiopterin (BH4) deficiency accounts for 1-3% of all reported forms of hyperphenylalaninaemia (HPA). Deficiencies of two enzymes, G TP-cyclohydrolase (GTPch; EC 3.5.4.16) and 6-pyruvoyl tetrahydropterin synthase (6-PTS), lead to a defect in BH4 biosynthesis. During the hy droxylation of phenylalanine (Phe) to tyrosine by phenylalanine hydrox ylase (PAH; EC 1.14.16.1), BH, is oxidized to quinonoid dihydrobiopter in (qBH2). In order to regenerate BH4, qBH2 is reduced by the enzyme d ihydropteridin reductase (DHPR; EC 1.6.99.7). More recently a new form (primapterinuria) due to a possible defect in the activity of dehydra tase has been described. Since BH4 is required as cofactor by PAH and by mammalian aromatic amino acid hydroxylases, a deficiency leads not only to HPA but also to a deficiency of biogenic amine neurotransmitte rs dopamine and serotonin (Blau 1988), its clinical picture and mode o f therapy would be expected to be different from the other types of HP A. This paper describes distinctive clinical and biochemical features of 16 BH4-deficient cases diagnosed and followed up at a single metabo lic unit.