Ornithine transcarbamylase deficiency is the most common urea cycle disorder.
Unlike the majority of metabolic enzyme deficiencies, ornithine transcarbamylase deficiency is inherited in an X-linked recessive fashion. This means that this disorder is more prevalent in males than females.
Because this enzyme deficiency causes a defect in the urea cycle, the body's ability to get rid of ammonia is affected and patients exhibit hyperammonemia. An important note regarding hyperammonemia in this disease is that the prognosis of disease is correlated to the length of exposure to high ammonia levels, rather than the level of ammonia. Thus, those who have been exposed to hyperammonemia for extended periods of time often have a worse clinical picture than those who may have had a very high level of ammonium for a short amount of time.
The buildup of orotic acid in ornithine transcarbamylase can often be confused with orotic aciduria, a disorder caused by a deficiency in a bifunctional protein that includes the activities of orotate phosphoribosyltransferase and orotidine 5' – phosphate decarboxylase in the pyrimidine synthesis pathway. The hereditary form of orotic aciduria can be distinguished from an increase in orotic acid secondary to an ornithine transcarbamylase deficiency by evaluating blood ammonia levels. In a urea cycle deficit caused by a defect in ornithine transcarbamylase, there will be hyperammonemia and decreased BUN.
Another result of this enzyme deficiency is the buildup of orotic acid in the blood. This occurs as the substrate carbamoyl phosphate enters the pyrimidine synthesis pathway and forms orotic acid.
In this disorder, the deficiency of the enzyme ornithine transcarbamylase leads to excess buildup of carbamoyl phosphate. As excess carbamoyl phosphate enters the pyrimidine synthesis pathway, it is converted to orotic acid, leading to an abnormal increase of orotic acid in the blood and urine.
This deficiency is often evident in the first few days of life with failure to thrive. Other early findings of ornithine transcarbamylase deficiency include irritability, vomiting, excessive somnolence, and uncontrolled body movements.
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