Orotic Acid, Urine

Urine, frozen

3 mL

0.5 mL (Note: This volume does not allow for repeat testing.)

Plastic urine container, no preservative

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.

This test was developed and its performance characteristics determined by LabCorp. It has not been cleared or approved by the Food and Drug Administration.

Liquid chromatography/tandem mass spectrometry (LC/MS-MS)

Orotic acid is an intermediary in the metabolism of the nucleotide pyrimidine, immediately following the conversion of carbamoyl phosphate to dihydroorotate in the human mitochondria. Orotic acid is then converted into orotate monophosphate by the activated form of ribose 5-phosphate, 5-phosphoribosyl-1-pyrophosphate, which is delivered in to the urea cycle. The urea cycle is of vital importance to the functions of the body, as it clears unused ammonia and its precursor metabolites through urinary excretions. Ammonia buildup (hyperammonemia) may rapidly develop, manifesting initially as lethargy and vomiting, eventually leading to cerebral edema, coma, and death. Other symptoms urea cycle disorders present include hyper- or hypoventilation, anorexia, hypothermia caused by a lack of thermoregulation, seizures, sleep disorders, delusions (in adult-onset hyperammonemia), and abnormal posturing of the body caused by swelling of the brain and pressure on the brain stem. Urea cycle disorders normally become apparent in early childhood, often a few days after birth, though late-onset variants of these disorders exist. Likewise, female carriers of the X-linked disorder ornithine transcarbamylase (OTC) deficiency may be symptomatic with a variable age of onset. Symptoms in late-onset forms are often triggered by excess stress and/or illness. Many children leave hospital care before defects of the urea cycle become apparent, emphasizing the need for diagnostic tools that provide clinically-relevant information before physical symptoms can present and cause irreversible damage.