Response of 6-pyruvoyl-tetrahydropterin synthase deficiency to tetrahydrobiopterin.

We have given tetrahydrobiopterin (BH4) in doses ranging from 2.5 to 20 mg/kg/day, each for a duration of 5 days to three patients with 6-pyruvoyltetrahydropterin synthase deficiency. As small a dose as 2.5 mg/kg/day BH4 reduced the blood phenylalanine to normal levels. However, the required dose of BH4 to reduce neopterin and to increase urine biopterin was 5 to 10 mg/kg/day, while 20 mg/kg/day was required for biopterin to appear in cerebrospinal fluid. The results suggest that BH4 effectively reduces endogenous neopterin synthesis. The dose of BH4 needed to normalize liver phenylalanine hydroxylase is one eighth to one fourth that required for normal neurotransmitter metabolism in the central nervous system.