General description

Ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle disorder, characterized by a metabolic defect in ammonia detoxification. Ammonia, produced during amino acid metabolism, is normally converted to urea in the liver through the urea cycle. In OTCD, a mutation in the OTC gene, which is X-linked semi-dominant, leads to the accumulation of ammonia and glutamine, resulting in hyperammonemia and associated encephalopathy.

Severe cases of OTCD primarily affect male neonates due to the X-linked inheritance pattern. These infants appear normal at birth but rapidly develop symptoms within 24–48 hours, including poor feeding, hypothermia, hyperventilation, lethargy, and apnea, which can quickly progress to coma or death if untreated. In contrast, mild cases may present at any age, from infancy to adulthood, with a wide range of symptoms, including vomiting, altered consciousness, ataxia, seizures, developmental delays, and chronic neurological issues. In females, who are more likely to experience late-onset OTCD, symptoms can range from asymptomatic carrier status to intermittent hyperammonemic crises. Chronic manifestations in both sexes may include intellectual disability, recurrent vomiting, feeding difficulties, and long-term neurological impairments.