|Classification and external resources|
Orotic aciduria refers to an excessive excretion of orotic acid in urine. It causes a characteristic form of anemia and may be associated with mental and physical retardation.
Orotic acid is an intermediate product in pyrimidine synthesis pathway, a subsequent product of which plays a role in conversion between dihydrofolate and tetrahydrofolate. Orotic aciduria is associated with megaloblastic anemia due to decreased pyrimidine synthesis, which leads to decreased nucleotide-lipid cofactors needed for erythrocyte membrane synthesis in the bone marrow.
Signs and symptoms
In addition to the characteristic excessive orotic acid in the urine, patients typically have megaloblastic anemia (UMP synthase def) which cannot be cured by administration of vitamin B12 or folic acid.
Cause and genetics
Its hereditary form, an autosomal recessive disorder, can be caused by a deficiency in the enzyme UMPS, a bifunctional protein that includes the enzyme activities of orotate phosphoribosyltransferase and orotidine 5'-phosphate decarboxylase.
It can also arise secondary to blockage of the urea cycle, particularly in ornithine transcarbamylase deficiency (or OTC deficiency). You can distinguish this increase in orotic acid secondary to OTC deficiency from hereditary orotic aciduria (seen above) by looking at blood ammonia levels and the BUN (blood urea nitrogen). In OTC deficiency, because the urea cycle backs up, you will see hyperammonemia and a decreased BUN.
- Balasubramaniam, S; Duley, JA; Christodoulou, J (Sep 2014). "Inborn errors of pyrimidine metabolism: clinical update and therapy.". Journal of inherited metabolic disease 37 (5): 687–98. doi:10.1007/s10545-014-9742-3. PMID 25030255.
- Huguley CM, Bain JA, Rivers SL, Scoggins RB (Jun 1959). "Refractory megaloblastic anemia associated with excretion of orotic acid". Blood 14 (6): 615–634. PMID 13651334.
- Winkler JK, Suttle DP (Jul 1988). "Analysis of UMP synthase gene and mRNA structure in hereditary orotic aciduria fibroblasts". Am J Hum Genet. 43 (1): 86–94. PMC 1715274. PMID 2837086.
- Suchi M, Mizuno H, Kawai Y, Tsuboi T, Sumi S, Okajima K, Hodgson ME, Ogawa H, Wada Y (Mar 1997). "Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families." (FREE FULL TEXT). American Journal of Human Genetics 60 (3): 525–539. ISSN 0002-9297. PMC 1712531. PMID 9042911.
- Orotic aciduria hereditary at NIH's Office of Rare Diseases
- Orotic aciduria purines-pyrimidines at NIH's Office of Rare Diseases