Different Strategies In the Treatment of Dihydropteridine Reductase Deficiency

Inherited deficiency of dihydropteridine reductase (DHPR, EC 1.66.99.7) impairs the regeneration of tetrahydrobiopterin (B H 4), the essential cofactor of phenylalanine (Phe) , tyrosine (Tyr), and trypthophan (Trp) hydroxylases, which is oxidized to qBH2 during a coupled reaction with these enzymes ( 1). Hyperphenylalaninemia and scarce production of monoamine neurotransmitters derived from Tyr and Trp-dopamine, norepinephrine, and serotonin-are the main metabolic derangements caused by DHPR deficiency. Untreated patients early develp a severe an progressive neurological picture , which is shared by other inborn errors of BH4 metabolism (1 ). The control of hyperphenylalaninemia and biogenic amine deficiency is necessary to improve their prognosis, together with folinic acid supplementation to avoid folate depiction (2 ) . DHPR deficiency, however, is a heterogeneous disease both at clinical and molecular level. The dietary tolerance to Phe is highe r than in classical phenyketonuria, but shows interindividual differences, as well as age-dependent increase ( 1 ). The control of hype rphenylalaninemia can be achieved either by a Phe-restricted diet or by administration of synthetic cofactor. As in these patients some recycling of BH4 do occur (3), a daily dosage of 8-20 mg/ kg is sufficient to attain nor-