Article Title

Orotic Aciduria


Orotic acid is an intermediate found in the pathway for pyrimidine synthesis. The mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) catalyzes the production of orotic acid by the conversion of the compound dihydroorotate to orotic acid. Orotic acid is commonly produced by this reaction in erythrocytes, hepatocytes, and kidney cells. Chemical modification of orotic acid in the pyrimidine pathway will generate nucleotides involved in DNA and RNA synthesis. Orotic aciduria can occur as a secondary manifestation due to a defect in an enzyme or transporter within the urea cycle, due to competitive inhibition by anti-cancer drugs such as allopurinol and 6-azauridine, or due to diseases such as Reye’s syndrome and mitochondrial disorders. The primary cause of orotic aciduria is a rare, autosomal recessive disorder in the family of inborn errors in metabolism, and can be categorized into three groups. Type I, II, and III orotic aciduria occur due to a genetic defect in the bifunctional enzyme uridine monophosphate synthase (UMPS). Neonatal patients diagnosed with this disorder commonly exemplify symptoms such as lethargy, difficulty feeding, and low birth weight and height. Neural and developmental deficits, megaloblastic anemia, and crystalluria may also occur. Laboratory findings typically include extremely high urinary orotic acid levels, megaloblastic anemia, and very low UMPS activity. Since early treatment with Xuriden may cause remission of symptoms, future studies should focus on improving early detection screening methods. Early diagnosis and treatment is clinically significant because impaired pyrimidine synthesis can lead to severe symptoms such as mental retardation, coma, or death.


Aliah Fonteh is a graduate student at Liberty University. After completing her B.S. in Biomedical Sciences at Liberty, Ms. Fonteh returned to complete her M.S. in Biomedical Sciences. After graduation in May 2019, her goal is to pursue a medical degree. As a practicing physician oneday, she dreams of offering medical care to underprivileged populations worldwide.

Aliah L. Fonteh