Treatment of phenylketonuria due to dihydropteridine reductase deficiency

Most cases of hyper-phenylalaninemia are due to deficiency of phenyl-alanine hydroxylase that converts phenyl-alanine to tyrosine. This enzymic reaction is facilitated by the co-factor tetrahydrobiopterin (BH4). A defect in the latter substrate leads to increased phenyl-alanine in 1-2 cases per million live births. Such cases are characterized by a degenerative brain process, and pronounced neurologic symptoms that cannot be prevented by a low phenyl-alanine diet alone. In 3 male newborns a deficiency of dihydropteridine reductase (DHPR) activity was diagnosed, the last of a sequence of 3 enzymes involved in the formation of BH4. Successful outcome of treatment, as well as the results of failure to diagnose and treat affected newborns, are described, with emphasis on the logistic problems involved in mass screening.