New approaches to the diagnosis and treatment of inborn errors of urea synthesis

Acute therapy of hyperammonemic coma continues to be a vexing problem. Peritoneal dialysis appears to be more effective than exchange transfusion in removing accumulated nitrogen. Hemodialysis, if immediately available, is also effective. Sodium benzoate alone has avoided the necessity for peritoneal dialysis in many patients. However, at ammonium levels greater than tenfold normal, the effects of sodium benzoate have been equivocal. Intravenous arginine alone is effective therapy in treatment of hyperammonemic coma in AL and possibly AS deficiency. Long-term therapy of urea cycle enzymopathies using dietary manipulation alone has had limited success. Exploitation of alternative pathways of waste nitrogen excretion appears to improve control of these disorders. Arginine supplementation alone is sufficient therapy for AL deficiency. Arginine, protein restriction, and benzoate appear to be successful in managing AS deficiency. Sodium benzoate and/or phenylacetic acid combined with dietary manipulations may improve the prognosis in OTC and CPS deficiencies, but the long-term effectiveness of these drugs has yet to be tested.