Long-term survival of patients with argininosuccinate synthetase deficiency.

OBJECTIVE: To monitor long-term survival and outcome of patients with neonatal-onset argininosuccinate synthetase deficiency (ASD) who were treated with specific therapeutic protocols designed to activate alternative pathways of waste nitrogen excretion.
DESIGN: Patients for this study included 24 infants born before 1990 and rescued from hyperammonemic coma caused by neonatal-onset ASD; they were referred to this center for enrollment in ongoing clinical studies of sodium benzoate, sodium phenylacetate, and sodium phenylbutyrate. Collaborating physicians throughout the United States and Canada provided information on survival, intellectual development, intercurrent hyperammonemic episodes, and anthropometric and biochemical measurements.
RESULTS: The cumulative survival rate was 87.5% at 5 years and 72% at 10 years of age. Survivors include 15 patients currently treated with high doses of sodium phenylbutyrate; two patients have withdrawn. Among the treated group, 11 are classified as severely to profoundly mentally retarded. The remaining four patients have IQ measurements in the borderline to mentally retarded range. All patients have had intercurrent hyperammonemic episodes; our data indicate that the frequency of the episodes has decreased with implementation of the current protocol. These patients are growth retarded, but most have height-for-weight z scores within 2 SD of the mean. Laboratory studies of plasma amino acids and of hematopoietic, renal, and hepatic function are within normal limits with the exception of slightly elevated serum aminotransferase values.
CONCLUSION: Our results indicate that these drugs are safe and that the current protocol improves survival rates. However, survival is accompanied by mental retardation, growth retardation, risk of hyperammonemic episodes, and the necessity of lifetime adherence to strict medication and dietary management.