The symptoms of citrullinemia seem to originate from the hyperammonemia rather than citrulline accumulation. Acute hyperammonemia may necessitate hemodialysis, which is more effective for lowering ammonia than peritoneal dialysis or arteriovenous hemofiltration. Sodium benzoate is given to conjugate glycine, a major amino acid that contributes ammonia to the urea cycle, forming hippurate, which is subsequently excreted in the urine. Intravenous arginine results in ammonia clearance by enhancing formation of citrulline in argininosuccinic acid synthetase deficiency or argininosuccinate in argininosuccinate lyase deficiency. Both of these metabolites are excreted in the urine and draw off excess nitrogen from ammonia. Patients who survive the initial presentation are placed on protein restriction. Patients with either defect having onset in the newborn period face a poor outcome and significant risk of neurological damage or demise.
Because the diagnosis and therapy of these metabolic disorders is complex, the pediatrician is strongly advised to manage the patient in close collaboration with a consulting pediatric metabolic disease specialist. It is recommended that parents travel with a letter of treatment guidelines from the patient’s physician.