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Hereditary orotic aciduria

MedGen UID:
472940
Concept ID:
C0220987
Disease or Syndrome
Synonyms: Hereditary Orotic Aciduria; hereditary orotic aciduria; OPRT and ODC deficiency; orotate phosphoribosyltransferase and OMP decarboxylase deficiency; orotate phosphoribosyltransferase and orotidylic decarboxylase deficiency; orotic aciduria; orotic aciduria 1; orotic aciduria II (formerly); orotic aciduria type 1; orotic aciduria without megaloblastic Anaemia; orotic aciduria without megaloblastic Anemia; oroticaciduria; oroticaciduria 1; orotidylic decarboxylase deficiency; orotidylic pyrophosphorylase and orotidylic decarboxylase deficiency; Ump synthase deficiency; UMP synthtase deficiency; UMPS; Umps deficiency; uridine monophosphate synthase deficiency; uridine monophosphate synthetase deficiency
SNOMED CT: Hereditary orotic aciduria (16242007)
 
Monarch Initiative: MONDO:0009797
OMIM®: 258900

Definition

Orotic aciduria is a rare autosomal recessive disorder characterized by megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy, and most cases appear to have a good prognosis. A minority of cases have additional features, particularly congenital malformations and immune deficiencies, which may adversely affect this prognosis (summary by Webster et al., 2001). Bailey (2009) stated that only 2 cases of orotic aciduria without megaloblastic anemia (OAWA) had been reported. [from OMIM]

Clinical features

From HPO
Hematuria
MedGen UID:
5488
Concept ID:
C0018965
Disease or Syndrome
The presence of blood in the urine. Hematuria may be gross hematuria (visible to the naked eye) or microscopic hematuria (detected by dipstick or microscopic examination of the urine).
Oroticaciduria
MedGen UID:
78642
Concept ID:
C0268128
Finding
An increased concentration of orotic acid in the urine.
Orotic acid crystalluria
MedGen UID:
480256
Concept ID:
C3278626
Finding
Formation of crystals owing to an increased concentration of orotic acid in the urine.
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Anisocytosis
MedGen UID:
66371
Concept ID:
C0221278
Finding
Abnormally increased variability in the size of erythrocytes.
Poikilocytosis
MedGen UID:
67451
Concept ID:
C0221281
Finding
The presence of abnormally shaped erythrocytes.
Hypochromia
MedGen UID:
87187
Concept ID:
C0333912
Finding
A qualitative impression that red blood cells have less color than normal when examined under a microscope, usually related to a reduced amount of hemoglobin in the red blood cells.
Pyrimidine-responsive megaloblastic anemia
MedGen UID:
867366
Concept ID:
C4021731
Disease or Syndrome
A type of megaloblastic anemia that improves upon administration of pyrimidine supplements such as uridylic acid and cytidylic acid.
Folate-unresponsive megaloblastic anemia
MedGen UID:
870827
Concept ID:
C4025287
Disease or Syndrome
A type of megaloblastic anemia that does not improve upon administration of folate. Since vitamin B12 acts by promoting recycling of folate, administration of vitamin B12 also does not improve this type of anemia.
Impaired T cell function
MedGen UID:
395415
Concept ID:
C1860127
Cell or Molecular Dysfunction
Abnormally reduced ability of T cells to perform their functions in cell-mediated immunity.
Reduced orotidine 5-prime phosphate decarboxylase level
MedGen UID:
892392
Concept ID:
C4025636
Finding
An abnormal decrease in orotidine 5'-phosphate decarboxylase level.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • Hereditary orotic aciduria

Recent clinical studies

Etiology

Balasubramaniam S, Duley JA, Christodoulou J
J Inherit Metab Dis 2014 Sep;37(5):687-98. Epub 2014 Jul 17 doi: 10.1007/s10545-014-9742-3. PMID: 25030255
D'Apolito O, Garofalo D, la Marca G, Dello Russo A, Corso G
J Chromatogr B Analyt Technol Biomed Life Sci 2012 Feb 1;883-884:155-60. Epub 2011 Oct 6 doi: 10.1016/j.jchromb.2011.09.054. PMID: 22019295
Sumi S, Suchi M, Kidouchi K, Morishita H, Ohba S, Wada Y
J Inherit Metab Dis 1997 Mar;20(1):104-5. doi: 10.1023/a:1005330127995. PMID: 9061575

Diagnosis

Wortmann SB, Chen MA, Colombo R, Pontoglio A, Alhaddad B, Botto LD, Yuzyuk T, Coughlin CR, Descartes M, Grűnewald S, Maranda B, Mills PB, Pitt J, Potente C, Rodenburg R, Kluijtmans LA, Sampath S, Pai EF, Wevers RA, Tiller GE; additional individual contributors
J Inherit Metab Dis 2017 May;40(3):423-431. Epub 2017 Feb 15 doi: 10.1007/s10545-017-0015-9. PMID: 28205048Free PMC Article
Med Lett Drugs Ther 2016 Mar 28;58(1491):e49. PMID: 27027693
Chen J, Bennett MJ
Methods Mol Biol 2010;603:445-51. doi: 10.1007/978-1-60761-459-3_43. PMID: 20077096
Salerno C, Crifò C
J Chromatogr B Analyt Technol Biomed Life Sci 2002 Dec 5;781(1-2):57-71. doi: 10.1016/s1570-0232(02)00533-0. PMID: 12450653
Imaeda M, Sumi S, Imaeda H, Suchi M, Kidouchi K, Togari H, Wada Y
Tohoku J Exp Med 1998 May;185(1):67-70. doi: 10.1620/tjem.185.67. PMID: 9710947

Therapy

Ramesh D, Vijayakumar BG, Kannan T
Eur J Med Chem 2020 Dec 1;207:112801. Epub 2020 Sep 5 doi: 10.1016/j.ejmech.2020.112801. PMID: 32927231
Nyhan WL, Gangoiti JA
Neuropediatrics 2016 Dec;47(6):408-409. Epub 2016 Aug 30 doi: 10.1055/s-0036-1587594. PMID: 27574833
Med Lett Drugs Ther 2016 Mar 28;58(1491):e49. PMID: 27027693
Fox RM, Wood MH, Royse-Smith D, O'Sullivan WJ
Am J Med 1973 Dec;55(6):791-8. doi: 10.1016/0002-9343(73)90260-x. PMID: 4753642
Soutter GB, Yu J, Lovric A, Stapleton T
Aust Paediatr J 1970 Mar;6(1):47-52. doi: 10.1111/j.1440-1754.1970.tb02858.x. PMID: 5520435

Prognosis

Wortmann SB, Chen MA, Colombo R, Pontoglio A, Alhaddad B, Botto LD, Yuzyuk T, Coughlin CR, Descartes M, Grűnewald S, Maranda B, Mills PB, Pitt J, Potente C, Rodenburg R, Kluijtmans LA, Sampath S, Pai EF, Wevers RA, Tiller GE; additional individual contributors
J Inherit Metab Dis 2017 May;40(3):423-431. Epub 2017 Feb 15 doi: 10.1007/s10545-017-0015-9. PMID: 28205048Free PMC Article
Sumi S, Suchi M, Kidouchi K, Morishita H, Ohba S, Wada Y
J Inherit Metab Dis 1997 Mar;20(1):104-5. doi: 10.1023/a:1005330127995. PMID: 9061575
BECROFT DM, PHILLIPS LI
Br Med J 1965 Feb 27;1(5434):547-52. doi: 10.1136/bmj.1.5434.547. PMID: 14243056Free PMC Article

Clinical prediction guides

Wortmann SB, Chen MA, Colombo R, Pontoglio A, Alhaddad B, Botto LD, Yuzyuk T, Coughlin CR, Descartes M, Grűnewald S, Maranda B, Mills PB, Pitt J, Potente C, Rodenburg R, Kluijtmans LA, Sampath S, Pai EF, Wevers RA, Tiller GE; additional individual contributors
J Inherit Metab Dis 2017 May;40(3):423-431. Epub 2017 Feb 15 doi: 10.1007/s10545-017-0015-9. PMID: 28205048Free PMC Article
Nyhan WL, Gangoiti JA
Neuropediatrics 2016 Dec;47(6):408-409. Epub 2016 Aug 30 doi: 10.1055/s-0036-1587594. PMID: 27574833
Weinberg ME, Roman MC, Jacob P, Wen M, Cheung P, Walker UA, Mulligan K, Schambelan M
PLoS One 2011 Feb 17;6(2):e14709. doi: 10.1371/journal.pone.0014709. PMID: 21379380Free PMC Article
Chen J, Bennett MJ
Methods Mol Biol 2010;603:445-51. doi: 10.1007/978-1-60761-459-3_43. PMID: 20077096
Suchi M, Mizuno H, Kawai Y, Tsuboi T, Sumi S, Okajima K, Hodgson ME, Ogawa H, Wada Y
Am J Hum Genet 1997 Mar;60(3):525-39. PMID: 9042911Free PMC Article

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