Carbamoyl Phosphate Synthase Deficiency




Ornithine transcarbamylase deficiency (OTCD), the most common of the urea cycle disorders, is a rare metabolic disorder, occurring in one out of every 80,000 births. OTC is a genetic disorder resulting in a mutated and ineffective form of the enzyme ornithine transcarbamylase.


Like other urea cycle disorders, OTC affects the body's ability to get rid of ammonia, a toxic breakdown product of the body's use of protein. As a result, ammonia accumulates in the blood causing hyperammonemia. This ammonia travels to the various organs of the body. Another symptom of OTC is a buildup of orotic acid in the blood. This is due to an anapleurosis that occurs with carbamoyl phosphate entering the pyrimidine synthesis pathway.


Ornithine transcarbamylase deficiency is an X-linked recessive disorder caused by a number of different mutations. Since the gene is on the X chromosome, females are primarily carriers while males with nonconservative mutations rarely survive past 72 hours of birth. Half of those survivors die in the first month, and half of the remaining by age 5.


Since the disease results in an inability to handle large amounts of nitrogen load, the treatment includes strategies to decrease the intake of nitrogen (low-protein diet), prevention of excessive body protein breakdown during acute illnesses (hydration and nutrition) and administration of medications scavenging nitrogen (sodium benzoate and sodium phenylbutyrate). Some patients may need to have supplemental amino acids (arginine, citrulline, valine, leucine, isoleucine).