Hyperphenylalaninaemia due to dihydropteridine reductase deficiency

Two siblings with increased levels of serum phenylalanine were detected by newborn screening. The older sibling deteriorated neurologically and mentally, despite early dietary control, and died at the age of 6 1/2 years. In the younger sibling phenylalanine hydroxylase activity in liver tissue was normal. Further investigations revealed increased concentrations of biopterin derivatives in the blood, a low excretion of 5-hydroxyindole acetic acid in the urine, and a dihydropteridine reductase deficiency as the cause of hyperphenylalaninaemia. The parents of the siblings showed 50% of the normal dihydropteridine reductase activity in their fibroblasts grown in culture. Neurotransmitter therapy was started in the second child at the age of 6 months and this was followed by distinct neurological and mental improvement.