MCID: DHY005
MIFTS: 38

Dihydropyrimidinuria

Categories: Genetic diseases, Rare diseases, Metabolic diseases

Aliases & Classifications for Dihydropyrimidinuria

MalaCards integrated aliases for Dihydropyrimidinuria:

Name: Dihydropyrimidinuria 54 50 25 56 13 69
Dihydropyrimidinase Deficiency 50 24 25 56 71 29 69
Dpys Deficiency 50 25 71
Dph Deficiency 50 25 71
Dihydropyrimidinuria Due to Dpys Deficiency 71
Dihydrouracil Amidohydrolase Deficiency 25
Dihydropyrimidinase 13
Dpysd 71

Characteristics:

Orphanet epidemiological data:

56
dihydropyrimidinuria
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype
approximately 12 patients have been reported (as of march 2010)
about half of individuals are asymptomatic and identified by newborn screening programs
high frequency in japan (2 in 20,000, 0.1%)
mutation carriers may show toxicity to 5-fluorouracil (5fu)


HPO:

32
dihydropyrimidinuria:
Onset and clinical course phenotypic variability
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 56  
Inborn errors of metabolism


Summaries for Dihydropyrimidinuria

NIH Rare Diseases : 50 the following summary is from orphanet, a european reference portal for information on rare diseases and orphan drugs.orpha number: 38874disease definitiondihydropyrimidinase (dpd) deficiency is a very rare pyrimidine metabolism disorder with a variable clinical presentation including gastrointestinal manifestations (feeding problems, cyclic vomiting, gastroesophageal reflux, malabsorption with villous atrophy), hypotonia, intellectual deficit, seizures, and less frequently growth retardation, failure to thrive, microcephaly and autism. asymptomatic cases are also reported. dpd deficiency increases the risk of 5-fu toxicity.visit the orphanet disease page for more resources. last updated: 2/29/2012

MalaCards based summary : Dihydropyrimidinuria, also known as dihydropyrimidinase deficiency, is related to dihydropyrimidine dehydrogenase deficiency and neuroblastoma, and has symptoms including seizures, lethargy and metabolic acidosis. An important gene associated with Dihydropyrimidinuria is DPYS (Dihydropyrimidinase), and among its related pathways/superpathways are Porphyrin and chlorophyll metabolism and beta-Alanine metabolism (KEGG). Affiliated tissues include testes, and related phenotype is Decreased shRNA abundance (Z-score < -2).

Genetics Home Reference : 25 Dihydropyrimidinase deficiency is a disorder that can cause neurological and gastrointestinal problems in some affected individuals. Other people with dihydropyrimidinase deficiency have no signs or symptoms related to the disorder, and in these individuals the condition can be diagnosed only by laboratory testing.

OMIM : 54
DPYS deficiency is an autosomal recessive inborn error of pyrimidine metabolism. Less than a dozen affected individuals have been reported. About half are asymptomatic, but rare patients with neurologic abnormalities have been reported. It is unclear whether or not these abnormalities are related to the enzymatic defect. Affected individuals theoretically could have severe toxicity after the administration of the antineoplastic drug 5-fluorouracil (5FU), although no cases have been reported (Hamajima et al., 1998; van Kuilenburg et al., 2007). See also dihydropyrimidine dehydrogenase deficiency (274270), a similar disorder. (222748)

UniProtKB/Swiss-Prot : 71 Dihydropyrimidinase deficiency: An autosomal recessive disorder of pyrimidine metabolism characterized by dihydropyrimidinuria. It is associated with a variable clinical phenotype characterized by epileptic or convulsive attacks, dysmorphic features and severe developmental delay, and congenital microvillous atrophy. Most patients are, however, asymptomatic.

Related Diseases for Dihydropyrimidinuria

Diseases related to Dihydropyrimidinuria via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 11)
id Related Disease Score Top Affiliating Genes
1 dihydropyrimidine dehydrogenase deficiency 30.7 DPYD DPYS
2 neuroblastoma 10.3
3 schizophrenia 10.1
4 polycystic kidney disease 9.9
5 down syndrome 9.9
6 endometriosis 9.8
7 chromophobe renal cell carcinoma 9.8
8 hepatocellular carcinoma 9.7
9 melanoma and neural system tumor syndrome 9.5 DPYD DPYS
10 cataract 17, multiple types 9.4 DPYD DPYS
11 multifocal dystonia 9.2 DPYD DPYS

Graphical network of the top 20 diseases related to Dihydropyrimidinuria:



Diseases related to Dihydropyrimidinuria

Symptoms & Phenotypes for Dihydropyrimidinuria

Symptoms via clinical synopsis from OMIM:

54

Head And Neck- Head:
plagiocephaly (1 patient)

Head And Neck- Face:
dysmorphic facial features (1 patient)

Skeletal- Hands:
hypoplastic phalanges (1 patient)

Neurologic- Central Nervous System:
seizures (about 50% of patients)
mental retardation (3 patients)
speech delay (1 patient)
extrapyramidal dyskinesias (1 patient)
pyramidal signs (1 patient)
more
Growth- Other:
growth retardation (1 patient)

Abdomen- Gastroin testinal:
low anal atresia (1 patient)

Skeletal- Feet:
hypoplastic phalanges (1 patient)
clubfoot (1 patient)

Laboratory- Abnormalities:
increased uracil and dihydrouracil in bodily fluids
increased thymine and dihydrothymine in bodily fluids


Clinical features from OMIM:

222748

Human phenotypes related to Dihydropyrimidinuria:

32 (show all 18)
id Description HPO Frequency HPO Source Accession
1 seizures 32 HP:0001250
2 lethargy 32 HP:0001254
3 metabolic acidosis 32 HP:0001942
4 talipes equinovarus 32 HP:0001762
5 intellectual disability 32 HP:0001249
6 plagiocephaly 32 HP:0001357
7 feeding difficulties in infancy 32 HP:0008872
8 anal atresia 32 HP:0002023
9 delayed speech and language development 32 HP:0000750
10 growth delay 32 HP:0001510
11 extrapyramidal dyskinesia 32 HP:0007308
12 abnormal pyramidal signs 32 occasional (7.5%) HP:0007256
13 abnormal facial shape 32 HP:0001999
14 short phalanx of finger 32 HP:0009803
15 abnormality of the cerebral white matter 32 HP:0002500
16 excessive daytime somnolence 32 HP:0001262
17 morphological abnormality of the pyramidal tract 32 HP:0002062
18 reduced dihydropyrimidine dehydrogenase activity 32 HP:0003654

GenomeRNAi Phenotypes related to Dihydropyrimidinuria according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-139 9.4 DPYD
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-148 9.4 DPYS
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-17 9.4 DPYD
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-184 9.4 DPYD
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-203 9.4 DPYS
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-204 9.4 DPYS
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-213 9.4 DPYD
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-59 9.4 DPYD
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-61 9.4 DPYS
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-84 9.4 DPYS
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-91 9.4 DPYD DPYS

Drugs & Therapeutics for Dihydropyrimidinuria

Search Clinical Trials , NIH Clinical Center for Dihydropyrimidinuria

Genetic Tests for Dihydropyrimidinuria

Genetic tests related to Dihydropyrimidinuria:

id Genetic test Affiliating Genes
1 Dihydropyrimidinase Deficiency 29 24 DPYS

Anatomical Context for Dihydropyrimidinuria

MalaCards organs/tissues related to Dihydropyrimidinuria:

39
Testes

Publications for Dihydropyrimidinuria

Articles related to Dihydropyrimidinuria:

(show all 11)
id Title Authors Year
1
Diagnosis of dihydropyrimidinase deficiency in a Chinese boy with dihydropyrimidinuria. ( 23732435 )
2013
2
Dihydropyrimidinase deficiency: the first feline case of dihydropyrimidinuria with clinical and molecular findings. ( 23430934 )
2012
3
HPLC/ESI tandem-MS of liquid urine or urine soaked filter-paper strips for the detection of thymine-uraciluria and dihydropyrimidinuria. ( 11783519 )
2000
4
[Dihydropyrimidinase deficiency (dihydropyrimidinuria)]. ( 9590033 )
1998
5
Population and family studies of dihydropyrimidinuria: prevalence, inheritance mode, and risk of fluorouracil toxicity. ( 9714435 )
1998
6
Dihydropyrimidinase deficiency: confirmation of the enzyme defect in dihydropyrimidinuria. ( 9266350 )
1997
7
Dihydropyrimidinuria without clinical symptoms. ( 8892031 )
1996
8
Possible prediction of adverse reactions to pyrimidine chemotherapy from urinary pyrimidine levels and a case of asymptomatic adult dihydropyrimidinuria. ( 9816152 )
1996
9
Dihydropyrimidinuria: the first case in Japan. ( 7660934 )
1994
10
Dihydropyrimidinuria: a new inborn error of pyrimidine metabolism. ( 1770794 )
1991
11
Dihydropyrimidinuria. ( 1976182 )
1990

Variations for Dihydropyrimidinuria

UniProtKB/Swiss-Prot genetic disease variations for Dihydropyrimidinuria:

71
id Symbol AA change Variation ID SNP ID
1 DPYS p.Thr68Arg VAR_002267
2 DPYS p.Gln334Arg VAR_002268 rs121964923
3 DPYS p.Trp360Arg VAR_002269 rs121964924
4 DPYS p.Gly435Arg VAR_002270 rs267606773
5 DPYS p.Arg490Thr VAR_002271

ClinVar genetic disease variations for Dihydropyrimidinuria:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 DPYS NM_001385.2(DPYS): c.1001A> G (p.Gln334Arg) single nucleotide variant Pathogenic rs121964923 GRCh37 Chromosome 8, 105440299: 105440299
2 DPYS NM_001385.2(DPYS): c.1303G> A (p.Gly435Arg) single nucleotide variant Pathogenic rs267606773 GRCh37 Chromosome 8, 105405152: 105405152
3 DPYS NM_001385.2(DPYS): c.1078T> C (p.Trp360Arg) single nucleotide variant Pathogenic rs121964924 GRCh37 Chromosome 8, 105440222: 105440222
4 DPYS NM_001385.2(DPYS): c.1235G> T (p.Arg412Met) single nucleotide variant Pathogenic rs267606774 GRCh37 Chromosome 8, 105436475: 105436475
5 DPYS NM_001385.2(DPYS): c.424-1G> A single nucleotide variant Pathogenic rs879851088 GRCh37 Chromosome 8, 105459732: 105459732

Expression for Dihydropyrimidinuria

Search GEO for disease gene expression data for Dihydropyrimidinuria.

Pathways for Dihydropyrimidinuria

GO Terms for Dihydropyrimidinuria

Biological processes related to Dihydropyrimidinuria according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 pyrimidine nucleoside catabolic process GO:0046135 9.26 DPYD DPYS
2 thymine catabolic process GO:0006210 9.16 DPYD DPYS
3 uracil catabolic process GO:0006212 8.96 DPYD DPYS
4 pyrimidine nucleobase catabolic process GO:0006208 8.62 DPYD DPYS

Sources for Dihydropyrimidinuria

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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