Ornithine Transcarbamylase Deficiency

Ornithine transcarbamylase deficiency (OTCD) is a hereditary metabolic disorder and the most common urea cycle disorder (UCD). This X-linked genetic condition affects ureagenesis, displaying variable phenotypic expressions. Homozygous males with severe neonatal onset typically exhibit symptoms such as hyperammonemia, respiratory alkalosis, and hypothermia. Additionally, late-onset manifestations can occur in males with partial deficiency and in heterozygous females.  In suspected individuals, genetic testing is usually confirmatory; however, studies have documented instances where routine Sanger sequencing of the ornithine transcarbamylase (OTC) gene did not identify any disease-causing variants. Furthermore, next-generation sequencing and UCD gene panels proved unhelpful in diagnosing these cases. This underscores the importance of clinical and biochemical suspicion in diagnosing this rare yet potentially devastating disorder.  This activity comprehensively examines the pathophysiology, clinical presentation, and diagnostic evaluation of OTCD. Emphasizing the pivotal role of an interprofessional team underscores the importance of collaborative management to optimize clinical outcomes and reduce the morbidity and mortality associated with this disease.