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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. OTCD 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 often becomes evident in the first few days of life, however it can present at middle age [1]. An infant with ornithine transcarbamylase deficiency may be lacking in energy (lethargic) or unwilling to eat, and have poorly-controlled breathing rate or body temperature. Some babies with this disorder may experience seizures or unusual body movements, or go into a coma. Complications from ornithine transcarbamylase deficiency may include developmental delay and mental retardation. Progressive liver damage, skin lesions, and brittle hair may also be seen. Other symptoms include irrational behavior (caused by encephalitis), mood swings, and poor performance in school.

In some affected individuals, signs and symptoms of ornithine transcarbamylase may be less severe, and may not appear until later in life. Some female carriers become symptomatic later in life in times of metabolic stress. This can happen as a result of anorexia, starvation, malnutrition, pregnancy or even (in at least one case) as a result of gastric bypass surgery. It is also possible for symptoms to be exacerbated by extreme trauma of many sorts, including, (at least in one case) adolescent pregnancy coupled with severe stomach flu.


Mutations in the OTC gene cause ornithine transcarbamylase deficiency. Ornithine transcarbamylase deficiency belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions that occurs in liver cells. It processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys.

In ornithine transcarbamylase deficiency, the enzyme that starts a specific reaction within the urea cycle is damaged or missing. The urea cycle cannot proceed normally, and nitrogen accumulates in the bloodstream in the form of ammonia. Ammonia is especially damaging to the nervous system, so ornithine transcarbamylase deficiency causes neurological problems as well as eventual damage to the liver.

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. Prognosis is less clear in cases of adult onset OTCD, as detection of the disease is almost universally post symptomatic [2].


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).

In cases where the OTC enzyme production is very low or non-existent and treatment consisting of low-protein diet and dietary supplementation are inadequate, liver transplant may become a treatment option.

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