Orotic Acid
Overview
Orotic acid measures an intermediate in pyrimidine biosynthesis that accumulates when the urea cycle enzyme ornithine transcarbamylase (OTC) is deficient or when pyrimidine synthesis is dysregulated. Normally converted to orotidine monophosphate by orotate phosphoribosyltransferase, excess orotic acid in urine indicates hereditary urea cycle disorders or hereditary orotic aciduria. Elevated urinary levels diagnose OTC deficiency (most common urea cycle disorder) and distinguish it from other nitrogen accumulation disorders; plasma levels lack clinical utility. Clinically, orotic aciduria testing confirms urea cycle defects in neonates with hyperammonemia.
Clinical Use Cases
- Diagnosing ornithine transcarbamylase (OTC) deficiency.
- Confirming hereditary orotic aciduria (uridine monophosphate synthase deficiency).
- Differentiating urea cycle disorders from organic acidemias.
- Monitoring treatment response in hereditary orotic aciduria.
Specimen Types
- Urine (first morning or 24-hour preferred).
- Plasma (research use only).
Measurement Methods
- Gas chromatography-mass spectrometry (GC-MS).
- Liquid chromatography-tandem mass spectrometry (LC-MS/MS).
- Cation-exchange chromatography.
Test Preparation and Influencing Factors
- No special preparation; avoid protein loading prior to testing.
- Allopurinol therapy causes false positive orotic aciduria.
- Acute hyperammonemia episodes maximize urinary excretion.
- Sample stability poor; refrigerate and test promptly.
Synonyms
- Orotic aciduria.
- Orotidine.