N-acetylglutamate synthase (NAGS) deficiency is an inborn error of the urea cycle. Onset may occur from the neonatal period to adulthood. The presentation ranges from early neonatal hyperammonemia with failure to feed, inability to maintain body temperature and drowsiness, to late onset hyperammonemia that may result in chronic gastrointestinal, neurological or psychiatric signs, sometimes triggered by infections or other stress. These symptoms can lead to coma and death in the most severe cases. Approximately half of reported cases have presented in the neonatal period. NAGS deficiency is clinically and biochemically indistinguishable from carbamylphosphate synthetase I (CPSI) deficiency. General treatments for NAGS deficiency are protein restriction, hypercaloric infusion and arginine supplementation, if needed. Hyperammonemia in NAGS deficiency may be effectively treated with N-carbamylglutamate.