Hereditary orotic aciduria

General Information (adopted from Orphanet):

Synonyms, Signs: OROTIC ACIDURIA I
OROTATE PHOSPHORIBOSYLTRANSFERASE AND OROTIDYLIC DECARBOXYLASE DEFICIENCY
URIDINE MONOPHOSPHATE SYNTHASE DEFICIENCY
OROTIDYLIC PYROPHOSPHORYLASE AND OROTIDYLIC DECARBOXYLASE DEFICIENCY
OAWA, INCLUDED
OPRT AND ODC DEFICIENCY
UMP SYNTHASE DEFICIENCY
UMPS DEFICIENCY OROTIC ACIDURIA WITHOUT MEGALOBLASTIC ANEMIA, INCLUDED
Oroticaciduria
Uridine monophosphate synthetase deficiency
Orotidylic decarboxylase deficiency
Number of Symptoms 37
OrphanetNr: 30
OMIM Id: 258900
ICD-10: D53.0
UMLs: C0220987
C0268130
MeSH: C537136
MedDRA: 10052621
Snomed: 16242007
69525003

Prevalence, inheritance and age of onset:

Prevalence: 20 cases [Orphanet]
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: AARSKOG SYNDROME, AUTOSOMAL DOMINANT
 -AARSKOG SYNDROME, AUTOSOMAL DOMINANT
Disorder of pyrimidine metabolism
 -Rare genetic disease
Vitamin B12- and folate-independent constitutional megaloblastic anemia
 -Rare genetic disease
 -Rare hematologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0000072) Hydroureter Frequent [Orphanet] 146 / 7739
2
 (HPO:0000790) Hematuria 106 / 7739
3
 (HPO:0000431) Wide nasal bridge Frequent [Orphanet] 290 / 7739
4
 (HPO:0000316) Hypertelorism Frequent [Orphanet] 644 / 7739
5
 (HPO:0000494) Downslanted palpebral fissures Frequent [Orphanet] 328 / 7739
6
 (HPO:0000357) Abnormal location of ears Frequent [Orphanet] 328 / 7739
7
 (HPO:0001263) Global developmental delay Occasional [HPO:probinson] 853 / 7739
8
 (HPO:0001385) Hip dysplasia Frequent [Orphanet] 242 / 7739
9
 (HPO:0001744) Splenomegaly Frequent [Orphanet] 337 / 7739
10
 (HPO:0006568) Increased hepatic glycogen content Frequent [Orphanet] 34 / 7739
11
 (HPO:0001508) Failure to thrive rare [HPO:skoehler] 454 / 7739
12
 (HPO:0001510) Growth delay 295 / 7739
13
 (HPO:0008388) Abnormality of the toenails Frequent [Orphanet] 28 / 7739
14
 (HPO:0001631) Atria septal defect rare [HPO:skoehler] 274 / 7739
15
 (HPO:0001629) Ventricular septal defect rare [HPO:skoehler] 316 / 7739
16
 (HPO:0001671) Abnormality of the cardiac septa 55 / 7739
17
 (HPO:0001643) Patent ductus arteriosus Frequent [Orphanet] 228 / 7739
18
 (HPO:0001889) Megaloblastic anemia 28 / 7739
19
 (HPO:0011273) Anisocytosis 8 / 7739
20
 (HPO:0003339) Pyrimidine-responsive megaloblastic anemia 1 / 7739
21
 (HPO:0004826) Folate-unresponsive megaloblastic anemia 1 / 7739
22
 (HPO:0005435) Impaired T cell function Occasional [HPO:probinson] 9 / 7739
23
 (HPO:0004447) Poikilocytosis 16 / 7739
24
 (HPO:0001903) Anemia Very frequent [Orphanet] 289 / 7739
25
 (HPO:0004337) Abnormality of amino acid metabolism Very frequent [Orphanet] 45 / 7739
26
 (HPO:0003218) Oroticaciduria 10 / 7739
27
 (HPO:0003526) Orotic acid crystalluria 1 / 7739
28
 (HPO:0003267) Reduced orotidine 5-prime phosphate decarboxylase activity 1 / 7739
29
 (HPO:0002205) Recurrent respiratory infections Frequent [Orphanet] 254 / 7739
30
 (HPO:0010978) Abnormality of immune system physiology Frequent [Orphanet] 148 / 7739
31
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
32
 (HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 949 / 7739
33
 (OMIM) T-cell dysfunction, variable (in some patients) 1 / 7739
34
 (OMIM) Low to normal reticulocyte count 1 / 7739
35
 (OMIM) Orotic acid urinary obstruction 1 / 7739
36
 (OMIM) Hypochromia 6 / 7739
37
 (MedDRA:10035530) Platelet count normal 9 / 7739

Associated genes:

UMPS;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) 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 ...
Diagnosis OMIM Rogers and Porter (1968) devised a screening test for orotic aciduria that is effective in detecting either homozygotes or heterozygotes.
Clinical Description OMIM The phenotypic features of orotic aciduria are megaloblastic anemia that is unresponsive to vitamin B12 and folic acid, hypochromic, microcytic circulating erythrocytes that persist with administration of iron or pyridoxine, large amounts of orotic acid in the urine, and ...
Molecular genetics OMIM Suchi et al. (1997) detected compound heterozygosity for mutations in the UMPS gene (613891.0001-613891.0002) in a Japanese patient with orotic aciduria who was originally described by Morishita et al. (1986). Expression of human UMPS cDNAs containing these mutations in ...
Population genetics OMIM Webster et al. (2001) stated that they knew of only 15 cases of orotic aciduria, of which 14 had been established by direct measurement of UMPS.