Orotic acid levels are evaluated in certain urea cycle defects including ornithine transcarbomoylase (OTC) deficiency, citrullinemia and argininosuccinic aciduria, as well as the transport disorders including lysinuric protein intolerance and HHH (hyperornithinemia-hyperammonemia-homocitrullinuria) syndrome. Orotic acid is also elevated in hereditary orotic aciduria, or uridine monophosphate synthase deficiency, an autosomal recessive disorder characterized by megaloblastic anemia and crystalluria. Urine orotic levels are determined by liquid chromatography/tandem mass spectrometry. For patients with hyperammonemia and a suspected urea cycle defect, this test is typically ordered in conjunction with plasma amino acids and urine organic acids.