Orotic aciduria: Difference between revisions
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==Cause and Genetics== |
==Cause and Genetics== |
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[[Image:Autorecessive.jpg|thumb|right|Orotic aciduria has an autosomal recessive of inheritance.]] |
[[Image:Autorecessive.jpg|thumb|right|Orotic aciduria has an autosomal recessive of inheritance.]] |
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Its hereditary form, an [[autosomal]] [[recessive]] disorder,<ref name="pmid2837068">{{cite journal |author=Winkler JK, Suttle DP |title=Analysis of UMP synthase gene and mRNA structure in hereditary orotic aciduria fibroblasts |journal=Am J Hum Genet. |volume=43 |issue=1 |pages=86–94 |year=1988 |pmid=2837086 |pmc= 1715274|month=Jul}}</ref> can be caused by a deficiency in the [[enzyme]] [[UMPS]],<ref name="pmid9042911">{{cite journal |pmid=9042911 |pmc=1712531 |year=1997 |month=Mar |author=Suchi M, Mizuno H, Kawai Y, Tsuboi T, Sumi S, Okajima K, Hodgson ME, Ogawa H, Wada Y |title=Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families. |volume=60 |issue=3 |pages=525–539 |issn=0002-9297 |journal=American Journal of Human Genetics |format=Free full text}}</ref> a bifunctional protein that includes the enzyme activities of [[orotate phosphoribosyltransferase]] and [[orotidine 5'-phosphate decarboxylase]]. |
Its hereditary form, an [[autosomal]] [[recessive]] disorder,<ref name="pmid2837068">{{cite journal |author=Winkler JK, Suttle DP |title=Analysis of UMP synthase gene and mRNA structure in hereditary orotic aciduria fibroblasts |journal=Am J Hum Genet. |volume=43 |issue=1 |pages=86–94 |year=1988 |pmid=2837086 |pmc= 1715274|month=Jul}}</ref> can be caused by a deficiency in the [[enzyme]] [[Uridine monophosphate synthetase|UMPS]],<ref name="pmid9042911">{{cite journal |pmid=9042911 |pmc=1712531 |year=1997 |month=Mar |author=Suchi M, Mizuno H, Kawai Y, Tsuboi T, Sumi S, Okajima K, Hodgson ME, Ogawa H, Wada Y |title=Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families. |volume=60 |issue=3 |pages=525–539 |issn=0002-9297 |journal=American Journal of Human Genetics |format=Free full text}}</ref> a bifunctional protein that includes the enzyme activities of [[orotate phosphoribosyltransferase]] and [[orotidine 5'-phosphate decarboxylase]]. |
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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. In OTC deficiency, because the urea cycle backs up, you will see hyperammonemia and a decreased BUN. |
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. In OTC deficiency, because the urea cycle backs up, you will see hyperammonemia and a decreased BUN. |
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Revision as of 01:49, 7 March 2013
| Orotic aciduria | |
|---|---|
| Specialty | Hematology  |
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
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
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. In OTC deficiency, because the urea cycle backs up, you will see hyperammonemia and a decreased BUN.
Treatment
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.
See also
References
- ^ Huguley CM, Bain JA, Rivers SL, Scoggins RB (1959). "Refractory megaloblastic anemia associated with excretion of orotic acid". Blood. 14 (6): 615–634. PMID 13651334.
{{cite journal}}: Cite has empty unknown parameter:|1=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Winkler JK, Suttle DP (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.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Suchi M, Mizuno H, Kawai Y, Tsuboi T, Sumi S, Okajima K, Hodgson ME, Ogawa H, Wada Y (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.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link)
External links
- Orotic aciduria hereditary at NIH's Office of Rare Diseases
- Orotic aciduria purines-pyrimidines at NIH's Office of Rare Diseases
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