Clinical Use: Orotic Acid is an evaluation of the differential diagnosis of hyperammonemia and hereditary orotic aciduria. The allopurinol test can be used to determine whether a female is heterozygous for X-linked OTC deficiency when an OTC deficient patient has been identified in her family.
Background: The urinary excretion of orotic acid, an intermediate in pyrimidine biosynthesis, is increased in some urea cycle defects particularly ornithine transcarbamoyl (OTC) deficiency 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 hyperammonemia. Hyperammonemia is a characteristic of all urea cycle defects, but orotic acid is elevated in only some. Orotic acid is also elevated in the transport defects of dibasic amino acids (lysinuric protein intolerance, and hyperornithinemia, hyperammonemia, homocitrullinuria [HHH] syndrome), and is greatly elevated in patients with hereditary orotic aciduria (uridine monophosphate synthase [UMPS] deficiency).

In OTC deficiency, an X-linked urea cycle disorder, carbamoyl phosphate accumulates and is alternatively metabolized to orotic acid.

Allopurinol inhibits orotidine monophosphate decarboxylase and when given to OTC carriers can cause accumulations in an otherwise normal orotic acid excretion. An allopurinol challenge followed by several determinations of a proband’s orotic acid excretion can be useful to identify the approximately 20% of OTC carriers whose mutations are not detected by genetic testing.

Reference Ranges:
Associated Diseases:
Patient Preparation: None required
Specimen Requirements: Urine sample – plain universal
Turnaround Time: 4 weeks
Additional Information:
Referred Test: Referred test
Location: Paediatric Metabolic Centre