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 alter native pathways of waste nitrogen excretion. Design: Patients for this study included 24 infants born before 1990 and rescued from hyperammo nemic coma caused by neonatal-onset ASD; they were referred to this ce nter for enrollment in ongoing clinical studies of sodium benzoate, so dium phenylacetate, and sodium phenylbutyrate. Collaborating physician s throughout the United States and Canada provided information on surv ival, intellectual development, intercurrent hyperammonemic episodes, and anthropometric and biochemical measurements. Results: The cumulati ve survival rate was 87.5% at 5 years and 72% at in years of age, Surv ivors include 15 patients currently treated with high doses of sodium phenylbutyrate; two patients have withdrawn, Among the treated group, it are classified as severely to profoundly mentally retarded, The rem aining four patients have IQ measurements in the borderline to mentall y retarded range. All patients have had intercurrent hyperammonemic ep isodes; our data indicate that the frequency of the episodes has decre ased with implementation of the current protocol, These patients are g rowth retarded, but most have height-for-weight z scores within 2 SD o f the mean, Laboratory studies of plasma amino acids and of hematopoie tic, renal, and hepatic function are within normal limits with the exc eption of slightly elevated serum aminotransferase values. Conclusion: Our results indicate that these drugs are safe and that the current p rotocol improves survival rates, However, survival is accompanied by m ental retardation, growth retardation, risk of hyperammonemic episodes , and the necessity of lifetime adherence to strict medication and die tary management.