Ornithine Transcarbamylase (OTC) Deficiency
The enzyme OTC combines carbamyl-phosphate that is produced by CPS1 with an amino acid called ornithine to make citrulline. Patients with complete OTC deficiency (the most severe type of this disorder) rapidly develop high levels of ammonia in the blood, soon after birth and develop symptoms any time before one week of age. Infants who are successfully rescued from this first crisis are at risk for repeated episodes of hyperammonemia. The OTC gene is located on the X-chromosome. Males have only one X-chromosome while females have two. Hence, the majority of patients with severe presentations of OTC deficiency are males. Females with one “abnormal OTC gene” and one “normal OTC gene” may not show any clinical evidence of the disorder; however 15% can show some symptoms or signs of the disease. Patients with partial OTC deficiency (milder type of OTC) can present at any time of life with a triggering event such as an infection or other stress. The rise in ammonia levels is generally lower in females with this disorder as compared to the males.
The diagnosis of OTC deficiency relies mostly on DNA analysis for mutations, however, in approximately 10% of patients a deleterious mutation cannot be found, requiring enzyme analysis on a liver biopsy to establish the diagnosis.
Treatment consists of restriction of protein intake, use of essential amino acid supplements, supplementation of L-citrulline, and diversion of nitrogen by alternate pathway therapy with sodium benzoate and/or sodium phenylbutyrate. Liver transplantation is indicated in hard to control severe cases.