The intended use of the urinary orotic acid test is to identify elevations of orotic acid in patients with folate malabsorption or hereditary orotic aciduria (uridine-5'- monophosphate synthase deficiency), and to aid in the differential diagnosis of hyperammonemia and urea cycle defects. Elevated excretion of orotic acid also has been observed in patients with Reye syndrome and patients receiving treatment with allopurinol or 6-azauridine. Orotic acid is an intermediate in the pyrimidine de novo synthetic pathway. Conditions such as urea cycle defects produce orotic aciduria by increasing the availability of its precursor, carbamylphosphate, resulting in increased production of orotic acid. Assessment of urinary orotic acid can aid in differentiating between ornithine transcarbamylase deficiency (elevated orotic acid) and carbamylphosphate synthetase deficiency (no elevation). Elevated orotic acid may be observed in other conditions with hyperammonemia such as lysinuric protein intolerance and hyperornithinemia-hyperammonemia-homocitrullinuria syndrome. Deficient activity of uridine-5'-monophosphate synthase produces orotic aciduria by preventing the conversion of orotic acid to orotidine-5'-monophosphate. Patients with this condition have megaloblastic anemia and orotic acid crystalluria. Folate malabsorption may be primary or can be secondary to celiac disease, treatment with some medications, or heavy alcohol use.