|Values are valid only on day of printing.|
Evaluation of the differential diagnosis of hyperammonemia and hereditary orotic aciduria
When orotic acid is measured after a protein load or administration of allopurinol, excretion of orotic acid is a very sensitive indicator of ornithine transcarbamylase (OTC) activity. An allopurinol challenge may be helpful in determining whether a female patient may be a carrier of an OTC mutation if molecular genetic testing was not informative.
The urinary excretion of orotic acid, an intermediate in pyrimidine biosynthesis, is increased in many urea cycle disorders and in a number of other disorders involving the metabolism of arginine. The determination of orotic acid can be useful to distinguish between various causes of elevated ammonia (hyperammonemia). Hyperammonemia is characteristic of all urea cycle disorders, but orotic acid is elevated in only some, including ornithine transcarbamylase deficiency, citrullinemia, and argininosuccinic aciduria. Orotic acid is also elevated in the transport defects of dibasic amino acids (lysinuric protein intolerance and hyperornithinemia, hyperammonemia, and homocitrullinuria [HHH] syndrome), and greatly elevated in patients with hereditary orotic aciduria (uridine monophosphate synthase [UMPS] deficiency).
Ornithine transcarbamylase (OTC) deficiency is an X-linked urea cycle disorder that affects both males and females due to random X-inactivation. It is thought to be the most common urea cycle disorder with an estimated incidence of 1:56,000. In OTC deficiency, carbamoyl phosphate accumulates and is alternatively metabolized to orotic acid. Allopurinol inhibits orotidine monophosphate decarboxylase and, when given to OTC carriers (who may have normal orotic acid excretion), can cause increased excretion of orotic acid. A carefully monitored allopurinol challenge followed by several determinations of a patient's orotic acid excretion can be useful to identify OTC carriers, as approximately 20% of OTC mutations are not detectable by current molecular genetic testing methods.
<2 weeks: 1.4-5.3 mmol/mol creatinine
2 weeks-1 year: 1.0-3.2 mmol/mol creatinine
2-10 years: 0.5-3.3 mmol/mol creatinine
> or =11 years: 0.4-1.2 mmol/mol creatinine
The value for the orotic acid concentration is reported. The interpretation of the result must be correlated with clinical and other laboratory findings.
Pregnant women will normally excrete up to twice the upper limit of the adult reference range.
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