The importance of these observations for practice is that late-onset presentations of urea cycle disease are often unrecognized and, as evidenced by case 2, may be fatal, despite as many as 52 symptom-free years. Early symptoms suggestive of a psychiatric disorder, such as confusion or combativeness, or neurologic manifestations, such as ataxia, may be followed by cerebral edema and herniation. Prompt recognition can avert such an outcome because there are effective treatments, including hemodialysis, intravenous arginine, and sodium benzoate/phenylacetate.1,2 Intuitively, one would expect that patients with late-onset disease had mutations that determined an enzyme with appreciable residual activity, and, therefore, would be relatively easy to treat once a diagnosis was made. This has been our experience. For example, in a boy with OTC deficiency who presented at 12½ years of age, normal levels of ammonia were achieved with intravenous arginine administration alone,3 and he has not had a further episode of hyperammonemia in 15 years of follow-up treatment with oral citrulline and only modest restriction of protein. The twins (cases 3 and 4) have not been restricted to a protein intake lower than 2 g/kg daily, have also received oral citrulline, and have had no episodes of hyperammonemic metabolic imbalance.