Test ID: OROT    
Orotic Acid, Random, Urine

Evaluation of the differential diagnosis of hyperammonemia and hereditary orotic aciduria

Sensitive indicator of ornithine transcarbamylase (OTC) activity after administration of allopurinol or a protein load to identify OTC carriers

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 (OTC) 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 is greatly elevated in patients with hereditary orotic aciduria (uridine monophosphate synthase [UMPS] deficiency).

OTC deficiency is an X-linked urea cycle disorder that affects both male patients and, due to random X-inactivation, female patients. 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. When orotic acid is measured after a protein load or administration of allopurinol, its excretion is a very sensitive indicator of OTC activity. 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 variant 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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