Hyperammonemia occurs in patients with inborn errors of metabolism involving the urea cycle that metabolizes endogenous and exogenous nitrogen into urea. Six enzymes are required for the conversion of ammonia to urea, and deficiencies in these enzymes or in transporters cause urea cycle disorders (UCDs) and the accumulation of ammonia and precursor metabolites. All UCDs except ornithine transcarbamylase (OTC) deficiency have an autosomal recessive inheritance pattern. The OTC gene is located on the X chromosome (Xp21.1), making its inheritance pattern X-linked. OTC deficiency is the most common UCD and has an estimated prevalence of 1 in 14,000. Approximately 60% of mutations identified in patients with OTC deficiency are found in infants, and OTC deficiency is associated with high mortality. The definitive therapy involves urgent liver transplantation. The other 40% of the mutations identified with OTC deficiency are mild and have a late-onset presentation phenotype. The clinical phenotype in patients with partial enzyme deficiency ranges from asymptomatic to intermittent symptoms to chronic symptoms, and these patients can present at any age. There is significant phenotypic heterogeneity in late-onset patients, even in patients from the same family with the same mutation. Some patients have episodic symptoms during periods of catabolic stress, following increased protein intake, or after the addition of certain medications such as valproic acid (Table 1). The laboratory hallmark of UCDs is an elevated plasma ammonia levels. Other tests required for the evaluation of these patients include plasma amino acids, carnitine, and organic acid levels and urine amino acid, organic acid, and orotic acid levels. In OTC deficiency, plasma levels of glutamine are elevated and citrulline and arginine levels are reduced. Urinary orotic acid and glutamine levels are elevated. A female carrier can be screened using the allopurinol load test. The allopurinol load stimulates the excretion of orotic acid and orotidine in urine. DNA analysis can be used to identify a specific gene mutation.