Atypical phenylketonuria with defective biopterin metabolism. Monotherapy with tetrahydrobiopterin or sepiapterin, screening und study of biosynthesis in man

Abstract

Administration of a single dose of tetrahydrobiopterin dihydrochloride, 10–20 mg/kg orally, to a patient with dihydrobiopterin deficiency led to disappearance of clinical symptoms for 4 days, normalization of urinary phenylalanine and serotonin and decrease of elevated neopterin for 2–3 days. A dose-dependent stimulation of serotonin production was observed. A similar effect was note with even lower doses of L-sepiapterin. The patient is now under monotherapy with tetrahydrobiopterin·2 HCl, 2.5 mg/kg daily. Other patients with this disease may not respond as well. Results of screening for tetrahydrobiopterin deficiency in 228 cases with hyperphenylalaninemia, including 140 newborns, are reported. There is evidence that biopterin biosynthesis in human kidney and liver proceeds via a dioxo compound and L-sepiapterin.