LONG-TERM TREATMENT OF GIRLS WITH ORNITHINE, TRANSCARBAMYLASE DEFICIENCY

Background Ornithine transcarbamylase is an X-linked mitochondrial enz yme that catalyzes the synthesis of citrulline from carbamoyl phosphat e and ornithine. A deficiency of this enzyme leads to hyperammonemia a nd hyperglutaminemia. In boys the disease is often fatal when its onse t occurs during the neonatal period, but it is milder when onset occur s later in childhood. Heterozygous girls may be normal or may have epi sodes of hyperammonemic encephalopathy and decline in cognitive functi on. We report here on the long-term outcome in girls with ornithine tr anscarbamylase deficiency enrolled in studies of treatments designed t o activate new pathways of waste-nitrogen excretion. Methods We studie d 32 girls (age, 1 to 17 years) with ornithine transcarbamylase defici ency who had had at least one episode of encephalopathy. The patients were assigned to treatment that consisted of sodium benzoate, alone or in combination with sodium phenylacetate or sodium phenylbutyrate, or sodium phenylbutyrate alone. Collaborating physicians provided clinic al, metabolic, and developmental data at specified intervals. Results Patients treated according to these protocols had greater than 90 perc ent survival at five years and maintained appropriate weight for heigh t. The frequency of hyperammonemic episodes decreased with increasing age and with sodium phenylacetate or sodium phenylbutyrate treatment. Although the mean IQ before treatment was in the low average range, 19 of the 23 girls in whom intelligence was tested longitudinally had st able test scores. Conclusions Girls with symptomatic ornithine transca rbamylase deficiency who are treated with drugs that activate new path ways of waste-nitrogen excretion have fewer hyperammonemic episodes an d a reduced risk of further cognitive decline. (C) 1996, Massachusetts Medical Society.