Abstract
Three male siblings were reported with hyperphenylalaninemia and moderate to severe progressive neurological illness. They were unresponsive to a low phenylalanine diet. Finally they were found to be deficient in dihydropteridine reductase in the cultured skin fibroblasts.
They were born of consanguineous parents (first cousins) and had similar clinical courses. Developmental delay and epileptic seizures were noticed between the ages of three months and two years. Urinary FeCl3 reactions were negative and serum phenylalanine levels were between high normal and 15 mg/dl. Phenylalanine load tests showed high peaks and delay in return to preload levels of serum phenylalanine. Low phenylalanine diets were ineffective on their clinical courses. The eldest brother died at the age of ten years from bronchopheumonia, and the second and the third broteer are still alive but moderately neurologically retarded.
Dihydropteridine reductase in fibroblasts were below ten percent of the average normal values in the second and the third child. Excretion of Urinary biopterin-like compounds was within normal range in the third child. 5-hydroxyindoleacetic acid and homovanillic acid in cerebrospinal fluid were lower than normal range in the second and the third child. The multiple foci of calcification-deposit were found in the brain in autopsy material, on the skull X-ray film or on the CT scanning film in all siblings. This pathological finding may be significant in this particular disorder.
