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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.

Signs and symptoms [edit]

In addition to the characteristic excessive orotic acid in the urine, patients typically have megaloblastic anemia which cannot be cured by administration of vitamin B12 or folic acid.^[1]

It also can cause inhibition of RNA and DNA synthesis and failure to thrive. This can lead to mental and physical retardation.

Cause and Genetics [edit]

Orotic aciduria has an autosomal recessive of inheritance.

Its hereditary form, an autosomal recessive disorder,^[2] can be caused by a deficiency in the enzyme UMPS,^[3] 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.

Treatment [edit]

Administration of cytidine monophosphate and uridine monophosphate reduces urinary orotic acid and the anemia.

Administration of uridine, which is converted to UMP, will bypass the metabolic block and provide the body with a source of pyrimidine.

References [edit]

^ 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.

External links [edit]

Orotic aciduria hereditary at NIH's Office of Rare Diseases
Orotic aciduria purines-pyrimidines at NIH's Office of Rare Diseases

This genetic disorder article is a stub. You can help Wikipedia by expanding it.

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English Journal

Sensitive and Selective Determination of Orotic Acid in Biological Specimens Using a Novel Fluorogenic Reaction.

Yin S1, Dragusha S, Ejupi V, Shibata T, Kabashima T, Kai M.
Journal of fluorescence.J Fluoresc.2015 May 31. [Epub ahead of print]
Orotic acid is an intermediate in the synthesis pathway of uridine-5'-monophosphate, and increases in body fluids of patients suffering from hereditary disorders such as orotic aciduria and hyperammonemia. In this study, we developed a spectrofluorometric method with or without high-performance liqu
PMID 26026930

Clinical outcomes and the mutation spectrum of the OTC gene in patients with ornithine transcarbamylase deficiency.

Choi JH1, Lee BH1, Kim JH1, Kim GH2, Kim YM3, Cho J1, Cheon CK3, Ko JM4, Lee JH5, Yoo HW1.
Journal of human genetics.J Hum Genet.2015 May 21. doi: 10.1038/jhg.2015.54. [Epub ahead of print]
Ornithine transcarbamylase (OTC) deficiency is an X-linked inborn error of the urea cycle that leads to the accumulation of ammonia, resulting in neurological deficits. This study was performed to describe the clinical outcomes, biochemical features and molecular spectra of patients with OTC deficie
PMID 25994866

Hyperammonemia-induced encephalopathy: A rare devastating complication of bariatric surgery.

Kromas ML1, Mousa OY1, John S1.
World journal of hepatology.World J Hepatol.2015 May 8;7(7):1007-11. doi: 10.4254/wjh.v7.i7.1007.
The clinical manifestations of hyperammonemia are usually easily identifiable to the clinician when associated with liver disease and lead to prompt diagnosis and treatment. However, hyperammonemia-induced encephalopathy is rare in adults in the absence of overt liver disease, thus diagnosis is ofte
PMID 25954483

Japanese Journal

ガスクロマトグラフィー/マススペクトロメトリーによって診断されたオロット酸尿症の黒毛和種牛の1例(内科学)

大場恵典,高須正規,西飯直仁 [他],細田祝,鬼頭克也,松本勇,張春花,北川均
The journal of veterinary medical science 69(3), 313-316, 2007-03-25
4ヵ月齢の黒毛和種牛がガスクロマトグラフィー/マススペクトメトリーによってオロット酸尿症と診断された.これまでに黒毛和種牛でオロット酸尿症の報告はない.下痢を呈し,ヘマトクリットは低く,小赤血球と棘状赤血球が観察された.低蛋白および高アンモニア血症を示し,尿沈渣に針状のオロット酸結晶を認めた.ウシuridine monophosphate synthaseのDNA解析ではサイレント変異のみを認めた …
NAID 110006241879