Ornithine Transcarbomylase Deficiency (OTC)

Ornithine transcarbomylase deficiency is a pan-ethnic disorder caused by pathogenic variants in the gene OTC. It is inherited in an X-linked manner, and therefore males are affected more often and more severely than females. Onset is typically in the first days of life. Affected males quickly develop an excess of ammonia in the blood, which causes vomiting, lethargy, and coma, and is fatal if not quickly treated. The longer that the patient experiences an excess of ammonia in the blood, the more severe the resulting brain damage will be. Although a low-protein diet is given as treatment, life-threatening recurrences can happen at any age. Many patients require liver transplants in infancy. Even with appropriate treatment, patients develop learning disabilities, intellectual disability, and/or attention deficit hyperactivity disorder. Onset may occur later in life, but episodes of hyperammonemia are as severe as those found in the early-onset form. While specific variants may be associated with early or late onset of the disease, variability can exist due to environmental conditions; for example, an illness in a newborn can trigger an attack, even when the individual has a variant associated with late-onset disease. Therefore, it is difficult to predict the age of onset based on the patient’s genotype.

For information about carrier frequency and residual risk, please see the Expanded Carrier Screen brochure.