Ornithine transcarbamylase deficiency (OTC), 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.

Symptoms

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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 including the brain, causing coma, brain damage and death.

Ornithine transcarbamylase deficiency often becomes evident in the first few days of life. 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.

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. This can happen as a result of anorexia, starvation, malnutrition, or even (in at least one case) as a result of gastric bypass surgery.

Genetics

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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 disorder. Since the mutation is on the X chromosome, females are primarily carriers while males rarely survive past 72 hours of birth. Half of those survivors die in the first month, and half of the remaining by age 5.

Treatment

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Treatment includes a low-protein formula called keto-acid and sodium benzoate, a preservative, and another type of sodium, which binds to ammonia and helps eliminate it from the body. Some treatment includes a protein limited diet combined with a dietary supplement including arginine.

Reference

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• National Library of Medicine Ornithine transcarbamylase deficiency

External links

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• Emedicine article

Inborn errors of metabolism | Genetic disorders