A sibling case of hyperphenylalaninemia due to a deficiency of dihydropteridine reductase: biochemical and pathological findings.

Three siblings with hyperphenylalaninemia were described, who showed convulsions and severe mental retardation despite dietary control of blood phenylalanine. The cultured skin fibroblasts from two patients revealed a markedly low activity of dihydropteridine reductase. These patients showed low levels of serum folate and of 5-hydroxyindoleacetic acid and homovanillic acid in cerebrospinal fluid. The postmortem examination on one of these siblings exhibited the dysmyelination in the cerebrum and spongy lesions of the white matter in the cerebellum, pons, medulla oblongata and spinal cord. Many minute foci of calcification were found in the cerebrum, which were located in the perivascular space of the small blood vessels. Such calcification was observed on CT scanning of the brain in the other two living siblings as well.