This leads to accumulation of alanine and glutamine, transamination products of pyruvate and glutamate, respectively, and, finally, of ammonia. The condition is progressive without intervention. Overall, the hepatic urea cycle is the major route for waste nitrogen disposal, generation of which is chiefly from protein and amino acid metabolism. Low-level synthesis of certain cycle intermediates in extrahepatic tissues makes a small contribution to waste nitrogen disposal as well. Overall, activity of the cycle is regulated by the rate of synthesis of NAG, the enzyme activator that initiates incorporation of ammonia into the cycle.
NAGS deficiency is associated with significant morbidity and mortality.
Patients who present with hyperammonemia are at risk for cerebral edema and death if treatment is not begun immediately. Case reports of NAGS deficiency have shown the condition to occur in both genders. As with many inherited metabolic diseases, the most likely time of presentation is in the newborn period. The multiple primary causes of hyperammonemia, specifically those due to urea cycle enzyme deficiencies, are somewhat variable in presentation, diagnostic features, and treatment. Combativeness Obtundation Coma Cerebral edema Death if treatment is not forthcoming or effective As a consequence, the most striking clinical findings of each urea cycle disorder relate to this constellation of symptoms and rough temporal sequence of events.