MCID: ORT008
MIFTS: 51

Orotic Aciduria

Categories: Genetic diseases, Rare diseases, Metabolic diseases, Blood diseases

Aliases & Classifications for Orotic Aciduria

MalaCards integrated aliases for Orotic Aciduria:

Name: Orotic Aciduria 53 12 71 36 28 13 51 14
Orotidylic Pyrophosphorylase and Orotidylic Decarboxylase Deficiency 53 49 71
Uridine Monophosphate Synthase Deficiency 53 49 71
Hereditary Orotic Aciduria 49 55 69
Umps Deficiency 53 49 71
Orotate Phosphoribosyltransferase and Orotidylic Decarboxylase Deficiency 53 71
Uridine Monophosphate Synthetase Deficiency 49 55
Oprt and Odc Deficiency 53 71
Ump Synthase Deficiency 53 71
Orotic Aciduria I 53 71
Oroticaciduria 1 49 71
Oroticaciduria 55 28
Orotate Phosphoribosyltransferase and Omp Decarboxylase Deficiency 49
Orotidylic Decarboxylase Deficiency 55
Hereditary Orotic Aciduria, Type 1 69
Orotic Aciduria Hereditary 51
Ump Synthtase Deficiency 49
Orotic Aciduria Type 1 49
Orotic Aciduria Ii 69
Orotic Aciduria 1 71
Orac1 71
Umps 49

Characteristics:

Orphanet epidemiological data:

55
hereditary orotic aciduria
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: any age;

OMIM:

53
Inheritance:
autosomal recessive


HPO:

31
orotic aciduria:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Orotic Aciduria

NIH Rare Diseases : 49 Orotic aciduria type I (OA1), also known as hereditary orotic aciduria, is a rare condition characterized by elevated levels of orotic acid in the urine. It typically becomes apparent in the first months of life with megaloblastic anemia, as well as delays in physical and intellectual development. OA1 is caused by changes (mutations) in the UMPS gene and inheritance is autosomal recessive. OA1 differs from other causes of orotic aciduria, which may include mitochondrial disorders, lysinuric protein intolerance, and liver disease. Treatment involves taking uridine; uridine triacetate was granted FDA approval for treating OA1 in 2015. Without treatment, children with OA1 may experience neutropenia, failure to thrive, developmental delay, and intellectual disability. Last updated: 9/13/2017

MalaCards based summary : Orotic Aciduria, also known as orotidylic pyrophosphorylase and orotidylic decarboxylase deficiency, is related to lysinuric protein intolerance and ornithine transcarbamylase deficiency, hyperammonemia due to, and has symptoms including hypertelorism, global developmental delay and hip dysplasia. An important gene associated with Orotic Aciduria is UMPS (Uridine Monophosphate Synthetase), and among its related pathways/superpathways are Pyrimidine metabolism and Carbon metabolism. Affiliated tissues include liver, t cells and testes, and related phenotype is integument.

OMIM : 53 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. (258900)

UniProtKB/Swiss-Prot : 71 Orotic aciduria 1: A disorder of pyrimidine metabolism resulting in megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. A minority of cases have additional features, particularly congenital malformations and immune deficiencies.

Disease Ontology : 12 A pyrimidine metabolic disorder that is characterized by an excessive secretion of orotic acid in urine.

Wikipedia : 72 Orotic aciduria is a disease yielding an excessive excretion of orotic acid in urine. It causes a... more...

Related Diseases for Orotic Aciduria

Graphical network of the top 20 diseases related to Orotic Aciduria:



Diseases related to Orotic Aciduria

Symptoms & Phenotypes for Orotic Aciduria

Symptoms via clinical synopsis from OMIM:

53
Laboratory Abnormalities:
hematuria
orotic acid crystalluria
orotic aciduria

Metabolic Features:
orotic aciduria

Cardiovascular Heart:
atrial septal defect (in 1 patient)
ventricular septal defect (in 1 patient)

Neurologic Central Nervous System:
developmental delay (in some patients)

Hematology:
megaloblastic anemia
poikilocytosis
anisocytosis
hypochromia
platelet count normal
more
Growth Other:
failure to thrive (in some patients)

Genitourinary:
orotic acid urinary obstruction

Immunology:
t-cell dysfunction, variable (in some patients)


Clinical features from OMIM:

258900

Human phenotypes related to Orotic Aciduria:

55 31 (show all 26)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 55 31 frequent (33%) Frequent (79-30%) HP:0000316
2 global developmental delay 55 31 occasional (7.5%) Very frequent (99-80%) HP:0001263
3 hip dysplasia 55 31 frequent (33%) Frequent (79-30%) HP:0001385
4 splenomegaly 55 31 frequent (33%) Frequent (79-30%) HP:0001744
5 recurrent respiratory infections 55 31 frequent (33%) Frequent (79-30%) HP:0002205
6 wide nasal bridge 55 31 frequent (33%) Frequent (79-30%) HP:0000431
7 aminoaciduria 55 31 hallmark (90%) Very frequent (99-80%) HP:0003355
8 anemia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001903
9 patent ductus arteriosus 55 31 frequent (33%) Frequent (79-30%) HP:0001643
10 low-set, posteriorly rotated ears 55 31 frequent (33%) Frequent (79-30%) HP:0000368
11 downslanted palpebral fissures 55 31 frequent (33%) Frequent (79-30%) HP:0000494
12 impaired t cell function 55 31 occasional (7.5%) Frequent (79-30%) HP:0005435
13 abnormality of the ureter 55 31 frequent (33%) Frequent (79-30%) HP:0000069
14 oroticaciduria 55 31 hallmark (90%) Very frequent (99-80%) HP:0003218
15 orotic acid crystalluria 55 31 hallmark (90%) Very frequent (99-80%) HP:0003526
16 failure to thrive 31 occasional (7.5%) HP:0001508
17 atrial septal defect 31 occasional (7.5%) HP:0001631
18 hematuria 31 HP:0000790
19 ventricular septal defect 31 occasional (7.5%) HP:0001629
20 abnormality of the toenails 55 Frequent (79-30%)
21 folate-unresponsive megaloblastic anemia 31 HP:0004826
22 poikilocytosis 31 HP:0004447
23 anisocytosis 31 HP:0011273
24 abnormal toenail morphology 31 frequent (33%) HP:0008388
25 reduced orotidine 5-prime phosphate decarboxylase activity 31 HP:0003267
26 pyrimidine-responsive megaloblastic anemia 31 HP:0003339

MGI Mouse Phenotypes related to Orotic Aciduria:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 integument MP:0010771 8.92 ASL ASS1 OTC SLC7A7

Drugs & Therapeutics for Orotic Aciduria

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Open-Label Study of Uridine Triacetate in Pediatric Patients With Hereditary Orotic Aciduria Completed NCT02110147 Phase 3 uridine triacetate

Search NIH Clinical Center for Orotic Aciduria

Genetic Tests for Orotic Aciduria

Genetic tests related to Orotic Aciduria:

# Genetic test Affiliating Genes
1 Orotic Aciduria 28 UMPS
2 Oroticaciduria 28

Anatomical Context for Orotic Aciduria

MalaCards organs/tissues related to Orotic Aciduria:

38
Liver, T Cells, Testes, Heart, B Cells

Publications for Orotic Aciduria

Articles related to Orotic Aciduria:

(show top 50) (show all 80)
# Title Authors Year
1
Mild orotic aciduria in UMPS heterozygotes: a metabolic finding without clinical consequences. ( 28205048 )
2017
2
Hereditary Orotic Aciduria and the Excretion of Orotidine. ( 27574833 )
2016
3
In brief: Uridine triacetate (Xuriden) for hereditary orotic aciduria. ( 27027693 )
2016
4
Hereditary Orotic Aciduria with Epilepsy and without Megaloblastic Anemia. ( 25757096 )
2015
5
A Caenorhabditis elegans model of orotic aciduria reveals enlarged lysosome-related organelles in embryos lacking umps-1 function. ( 20148972 )
2010
6
Orotic aciduria and uridine monophosphate synthase: a reappraisal. ( 19562503 )
2009
7
Japanese black cattle with orotic aciduria detected by gas-chromatography/mass-spectrometry. ( 17409652 )
2007
8
Orotic aciduria and plasma urea cycle-related amino acid alterations in short bowel syndrome, evoked by an arginine-free diet. ( 15449570 )
2004
9
Decreased fluorouracil cytotoxic effect on EB-virus transformed lymphocytes from hereditary orotic aciduria. ( 10851269 )
2000
10
Uracil phosphoribosyltransferase activity in hereditary orotic aciduria. ( 10404744 )
1999
11
Hereditary orotic aciduria heterozygotes accompanied with neurological symptoms. ( 9710947 )
1998
12
Mutation of ornithine transcarbamylase (H136R) in a girl with severe intermittent orotic aciduria but normal enzyme activity. ( 9266387 )
1997
13
Nutritional and metabolic effects and significance of mild orotic aciduria during dietary supplementation with arginine or its organic salts after trauma injury in rats. ( 9225832 )
1997
14
Pyrimidine metabolism in hereditary orotic aciduria. ( 9061575 )
1997
15
Benign persistent orotic aciduria and the possibility of misdiagnosis of ornithine carbamoyltransferase deficiency. ( 9266354 )
1997
16
A rapid and simple screening method for detection of orotic aciduria by capillary zone electrophoresis. ( 9086295 )
1997
17
Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families. ( 9042911 )
1997
18
Nucleotide pool imbalances in the livers of patients with urea cycle disorders associated with increased levels of orotic aciduria. ( 7773204 )
1995
19
Decreased hyperammonaemia and orotic aciduria due to inactivation of ornithine aminotransferase in mice with a hereditary abnormal ornithine carbamoyltransferase. ( 7707692 )
1994
20
Quantitative analysis of amniotic fluid pyrimidines for the prenatal diagnosis of hereditary orotic aciduria. ( 8295404 )
1993
21
Mild orotic aciduria and uricosuria in severe trauma victims. ( 1902349 )
1991
22
Urinary excretion of purines in sheep with experimental orotic aciduria. ( 1907065 )
1991
23
First report of management and outcome of pregnancies associated with hereditary orotic aciduria. ( 1776631 )
1991
24
Orotic aciduria fibroblasts express a labile form of UMP synthase. ( 2475503 )
1989
25
Hypogammaglobulinemia in orotic aciduria. ( 2754565 )
1989
26
Orotic aciduria due to arginine deprivation: changes in the levels of carbamoyl phosphate and of other urea cycle intermediates in mouse liver. ( 2778543 )
1989
27
Uridine-responsive hypogammaglobulinemia and congenital heart disease in a patient with hereditary orotic aciduria. ( 3183846 )
1988
28
Urinary purines, pyrimidines and nucleosides in uridine-treated orotic aciduria. ( 3390959 )
1988
29
Hepatic encephalopathy and orotic aciduria associated with hepatocellular carcinoma in a noncirrhotic liver. ( 2828214 )
1988
30
Analysis of UMP synthase gene and mRNA structure in hereditary orotic aciduria fibroblasts. ( 2837086 )
1988
31
An arginine-deficient diet in humans does not evoke hyperammonemia or orotic aciduria. ( 3668688 )
1987
32
Increase of protein synthesis by uridine supplement in lectin-stimulated peripheral blood lymphocytes and EB virus-transformed B cell line of hereditary orotic aciduria type I. ( 2829387 )
1987
33
Deficiency of UMP synthase in dairy cattle: a model for hereditary orotic aciduria. ( 2448544 )
1987
34
Effect of glycine on the induction of orotic aciduria and urinary bladder tumorigenesis in the rat. ( 3616403 )
1987
35
Hereditary orotic aciduria: further biochemistry. ( 3487927 )
1986
36
The role of hepatic ornithine transcarbamylase deficiency in the orotic aciduria of pregnant mice. ( 3732588 )
1986
37
Orotic aciduria, homocystinuria, formiminoglutamic aciduria and megaloblastosis associated with the formiminotransferase/cyclodeaminase deficiency. ( 3728187 )
1986
38
Orotic aciduria and species specificity. ( 6384838 )
1984
39
Absence of immune deficiency in hereditary orotic aciduria. ( 6717503 )
1984
40
Hereditary orotic aciduria: a defect of pyrimidine metabolism with cellular immunodeficiency. ( 6606448 )
1983
41
Cellular immune deficiency in two siblings with hereditary orotic aciduria. ( 6828110 )
1983
42
Hereditary orotic aciduria, Lesch-Nyhan syndrome, and xeroderma pigmentosum probed by herpes simplex virus: 125I-iododeoxycytidine incorporation as an assay for viral growth. ( 6826658 )
1983
43
Neonatal diagnosis of orotic aciduria: an experience with one family. ( 6848734 )
1983
44
Argininemia: report of a new case and mechanisms of orotic aciduria and hyperammonemia. ( 7164892 )
1982
45
Orotic aciduria caused by feeding excess lysine to growing rats. ( 6793701 )
1981
46
Orotic aciduria in lysinuric protein intolerance: dependence on the urea cycle intermediates. ( 7254935 )
1981
47
Purine and pyrimidine metabolism in hereditary orotic aciduria: some unexpected effects of allopurinol. ( 6775961 )
1980
48
Orotic aciduria and increased nitrogen catabolism in rats. ( 501442 )
1979
49
Amino acid induced orotic aciduria. ( 632945 )
1978
50
Factors affecting amino acid induced orotic aciduria in rats. ( 722348 )
1978

Variations for Orotic Aciduria

UniProtKB/Swiss-Prot genetic disease variations for Orotic Aciduria:

71
# Symbol AA change Variation ID SNP ID
1 UMPS p.Arg96Gly VAR_006807 rs121917890
2 UMPS p.Val109Gly VAR_006808 rs121917892
3 UMPS p.Gly429Arg VAR_006810 rs121917891

ClinVar genetic disease variations for Orotic Aciduria:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 UMPS NM_000373.3(UMPS): c.326T> G (p.Val109Gly) single nucleotide variant Pathogenic rs121917892 GRCh37 Chromosome 3, 124456430: 124456430
2 UMPS NM_000373.3(UMPS): c.638G> C (p.Gly213Ala) single nucleotide variant drug response rs1801019 GRCh37 Chromosome 3, 124456742: 124456742

Expression for Orotic Aciduria

Search GEO for disease gene expression data for Orotic Aciduria.

Pathways for Orotic Aciduria

Pathways related to Orotic Aciduria according to KEGG:

36
# Name Kegg Source Accession
1 Pyrimidine metabolism hsa00240

GO Terms for Orotic Aciduria

Biological processes related to Orotic Aciduria according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular amino acid biosynthetic process GO:0008652 9.33 ASL ASS1 OTC
2 cellular amino acid metabolic process GO:0006520 9.32 OTC SLC7A7
3 arginine biosynthetic process via ornithine GO:0042450 9.26 ASL OTC
4 urea cycle GO:0000050 9.13 ASL ASS1 OTC
5 arginine biosynthetic process GO:0006526 8.8 ASL ASS1 OTC

Molecular functions related to Orotic Aciduria according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lyase activity GO:0016829 8.96 ASL UMPS
2 amino acid binding GO:0016597 8.62 ASS1 OTC

Sources for Orotic Aciduria

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
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36 KEGG
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41 MeSH
42 MESH via Orphanet
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54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
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70 UMLS via Orphanet
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