MCID: DHY002
MIFTS: 54

Dihydropyrimidine Dehydrogenase Deficiency malady

Genetic diseases, Rare diseases, Metabolic diseases categories

Aliases & Classifications for Dihydropyrimidine Dehydrogenase Deficiency

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Sources:
45OMIM, 9Disease Ontology, 10diseasecard, 41NIH Rare Diseases, 20GeneTests, 21Genetics Home Reference, 11DISEASES, 47Orphanet, 22GTR, 60UMLS, 55SNOMED-CT, 38NCIt, 33MeSH, 34MESH via Orphanet, 26ICD10 via Orphanet, 61UMLS via Orphanet
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Dihydropyrimidine Dehydrogenase Deficiency, Aliases & Descriptions:

Name: Dihydropyrimidine Dehydrogenase Deficiency 45 9 41 21 11 47 60
Dihydropyrimidine Dehydrogenase 10 20 22
5-Fluorouracil Toxicity 45 10 47
Hereditary Thymine-Uraciluria 41 21
Familial Pyrimidinemia 41 47
Dihydropyrimidinuria 21 60
 
Dpd Deficiency 41 21
Dihydrouracil Dehydrogenase Deficiency 9
Familial Pyrimidinaemia 9
Familial Pyrimidemia 21
Thymine-Uracilurea 9


Classifications:



External Ids:

OMIM45 274270
Disease Ontology9 DOID:14218
NCIt38 C3964
MeSH33 D054067
SNOMED-CT55 238016000, 77365006
Orphanet47 1675, 240839
MESH via Orphanet34 D054067
ICD10 via Orphanet26 E79.8, T45.1
UMLS via Orphanet61 C1959620

Summaries for Dihydropyrimidine Dehydrogenase Deficiency

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NIH Rare Diseases:41 Dihydropyrimidine dehydrogenase (dpd) deficiency is a condition in which the body cannot break down the nucleotides thymine and uracil. dpd deficiency can have a wide range of severity; some individuals may have various neurological problems, while others have no signs and symptoms. signs and symptoms in severely affected individuals begin in infancy and may include seizures, intellectual disability, microcephaly, increased muscle tone (hypertonia), delayed motor skills, and autistic behavior.  all individuals with the condition, regardless of the presence or severity of symptoms, are at risk for severe, toxic reactions to drugs called fluoropyrimidines which are used to treat cancer. individuals with no symptoms may be diagnosed only by laboratory testing or after exposure to fluoropyrimidines. dpd deficiency is caused by mutations in the dpyd gene and is inherited in an autosomal recessive manner. last updated: 8/20/2012

MalaCards based summary: Dihydropyrimidine Dehydrogenase Deficiency, also known as dihydropyrimidine dehydrogenase, is related to pancreatic cancer and lung cancer, and has symptoms including agenesis of corpus callosum, autosomal recessive inheritance and microcephaly. An important gene associated with Dihydropyrimidine Dehydrogenase Deficiency is DPYD (dihydropyrimidine dehydrogenase), and among its related pathways are Cell Cycle / Checkpoint Control and beta-Alanine metabolism. The compounds pyrimidine analogues and tegafur-uracil have been mentioned in the context of this disorder. Affiliated tissues include testes, bone marrow and bone.

Disease Ontology:9 A purine-pyrimidine metabolic disorder that is an autosomal recessive metabolic disorder in which there is absent or significantly decreased activity of dihydropyrimidine dehydrogenase, an enzyme involved in the metabolism of uracil and thymine.

Genetics Home Reference:21 Dihydropyrimidine dehydrogenase deficiency is a disorder characterized by a wide range of severity, with neurological problems in some individuals and no signs or symptoms in others.

OMIM:45 Dihyropyrimidine dehydrogenase deficiency shows large phenotypic variability, ranging from no symptoms to a convulsive... (274270) more...

Wikipedia:63 Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) is an autosomal recessivemetabolic disorder... more...

Related Diseases for Dihydropyrimidine Dehydrogenase Deficiency

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Diseases related to Dihydropyrimidine Dehydrogenase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 49)
idRelated DiseaseScoreTop Affiliating Genes
1pancreatic cancer30.9DPYD, TYMS
2lung cancer30.8TYMS, DPYD, COL11A1
3neutropenia30.6TYMS, DPYD
4gallbladder cancer30.5TYMS, DPYD
5gastrointestinal carcinoma30.5DPYD, TYMS
6colorectal cancer30.5COL11A1, DPYD, TYMS
7pancreatitis10.6
8hepatitis10.6
9oral squamous cell carcinoma10.6
10hepatocellular carcinoma10.5
11cervicitis10.5
12esophageal cancer10.4
13renal cell carcinoma10.4
14esophagitis10.4
15prostate cancer10.3
16cholangiocarcinoma10.3
17intrahepatic cholangiocarcinoma10.3
18prostatitis10.3
19breast cancer10.3
20dihydropyrimidinuria10.3
21anaplastic large cell lymphoma10.3
22cicatricial ectropion10.3
23osteogenesis imperfecta10.3
24ectropion10.3
25gangliosidosis10.3
26biliary tract neoplasm10.2TYMS, DPYD
27nasopharyngeal carcinoma10.2
28pancreatic ductal adenocarcinoma10.2
29herpes zoster10.2
30nasopharyngitis10.2
31adenoiditis10.2
32sarcoma10.2
33thymoma10.2
34soft tissue sarcoma10.2
35hypotonia10.2
36stomatitis10.2TYMS, DPYD
37rectal neoplasm10.2DPYD, TYMS
38leukopenia10.1TYMS, DPYD
39diarrhea10.1TYMS, DPYD
40adenocarcinoma10.1
41lactic acidosis10.1
42deafness nephritis anorectal malformation10.1
43brain disease10.1ADSL, DPYD
44gastric adenocarcinoma10.1DPYD, TYMS
45cervical cancer, somatic10.0DPYD, TYMS
46epilepsy syndrome10.0ADSL, DPYD
47metabolic syndrome x9.9DPYD, ADSL
48squamous cell carcinoma, head and neck9.9DPYD, TYMS
49tongue squamous cell carcinoma9.7COL11A1, DPYD, TYMS

Graphical network of the top 20 diseases related to Dihydropyrimidine Dehydrogenase Deficiency:



Diseases related to dihydropyrimidine dehydrogenase deficiency

Symptoms for Dihydropyrimidine Dehydrogenase Deficiency

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Symptoms by clinical synopsis from OMIM:

274270

Clinical features from OMIM:

274270

HPO human phenotypes related to Dihydropyrimidine Dehydrogenase Deficiency:

(show all 22)
id Description Frequency HPO Source Accession
1 agenesis of corpus callosum rare (5%) HP:0001274
2 autosomal recessive inheritance HP:0000007
3 microcephaly HP:0000252
4 microphthalmos HP:0000568
5 coloboma HP:0000589
6 nystagmus HP:0000639
7 optic atrophy HP:0000648
8 autism HP:0000717
9 delayed speech and language development HP:0000750
10 hyperactivity HP:0000752
11 intellectual disability HP:0001249
12 seizures HP:0001250
13 muscular hypotonia HP:0001252
14 lethargy HP:0001254
15 motor delay HP:0001270
16 hypertonia HP:0001276
17 failure to thrive HP:0001508
18 growth delay HP:0001510
19 cerebral atrophy HP:0002059
20 tetraplegia HP:0002445
21 reduced dihydropyrimidine dehydrogenase activity HP:0003654
22 phenotypic variability HP:0003812

Drugs & Therapeutics for Dihydropyrimidine Dehydrogenase Deficiency

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Drug clinical trials:

Search ClinicalTrials for Dihydropyrimidine Dehydrogenase Deficiency

Search NIH Clinical Center for Dihydropyrimidine Dehydrogenase Deficiency

Genetic Tests for Dihydropyrimidine Dehydrogenase Deficiency

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Genetic tests related to Dihydropyrimidine Dehydrogenase Deficiency:

id Genetic test Affiliating Genes
1 Dihydropyrimidine Dehydrogenase Deficiency20 22 DPYD

Anatomical Context for Dihydropyrimidine Dehydrogenase Deficiency

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MalaCards organs/tissues related to Dihydropyrimidine Dehydrogenase Deficiency:

31
Testes, Bone marrow, Bone, Breast

Animal Models for Dihydropyrimidine Dehydrogenase Deficiency or affiliated genes

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Publications for Dihydropyrimidine Dehydrogenase Deficiency

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Articles related to Dihydropyrimidine Dehydrogenase Deficiency:

(show top 50)    (show all 78)
idTitleAuthorsYear
1
Tegafur-uracil (UFT) in lower doses is safe for the treatment of colorectal cancer in patients with partial dihydropyrimidine dehydrogenase deficiency: a proof of principle. (23323151)
2013
2
Evaluation of predictive tests for screening for dihydropyrimidine dehydrogenase deficiency. (23856855)
2013
3
Detection of complete dihydropyrimidine dehydrogenase deficiency in a Tunisian family using a simple phenotypic test. (24014927)
2013
4
Tegafur-uracil is a safe alternative for the treatment of colorectal cancer in patients with partial dihydropyrimidine dehydrogenase deficiency: a proof of principle. (22754590)
2012
5
Severe bone marrow suppression during adjuvant chemotherapy for gastric cancer by S-1 and its possible relationship to dihydropyrimidine dehydrogenase deficiency]. (20087047)
2010
6
Dihydropyrimidine dehydrogenase deficiency and toxicity to fluoropyrimidine]. (20146975)
2010
7
Analysis of severely affected patients with dihydropyrimidine dehydrogenase deficiency reveals large intragenic rearrangements of DPYD and a de novo interstitial deletion del(1)(p13.3p21.3). (19296131)
2009
8
Dihydropyrimidine dehydrogenase deficiency presenting with psychomotor retardation in the first Polish patient. (19081848)
2008
9
Detection of dihydropyrimidine dehydrogenase deficiency before treatment by fluoropyrimidines]. (17582309)
2007
10
DIHYDROPYRIMIDINE DEHYDROGENASE DEFICIENCY (DPD) IN GI MALIGNANCIES: EXPERIENCE OF 4-YEARS. (18846242)
2007
11
A pivotal role for beta-aminoisobutyric acid and oxidative stress in dihydropyrimidine dehydrogenase deficiency? (17065072)
2006
12
Increased prevalence of dihydropyrimidine dehydrogenase deficiency in African-Americans compared with Caucasians. (17000684)
2006
13
Hand-foot syndrome variant in a dihydropyrimidine dehydrogenase-deficient patient treated with capecitabine. (17026792)
2006
14
Profiling dihydropyrimidine dehydrogenase deficiency in patients with cancer undergoing 5-fluorouracil/capecitabine therapy. (17241513)
2006
15
Is capecitabine safe in patients with gastrointestinal cancer and dihydropyrimidine dehydrogenase deficiency? (16512996)
2006
16
Unpredicted severe toxicity after 5-fluorouracil treatment due to dihydropyrimidine dehydrogenase deficiency. (16646564)
2006
17
Methylation of the DPYD promoter: an alternative mechanism for dihydropyrimidine dehydrogenase deficiency in cancer patients. (16361556)
2005
18
Rapid identification of dihydropyrimidine dehydrogenase deficiency by using a novel 2-13C-uracil breath test. (15102667)
2004
19
Dihydropyrimidine dehydrogenase deficiency, a pharmacogenetic syndrome associated with potentially life-threatening toxicity following 5-fluorouracil administration. (15377401)
2004
20
Lethal toxicity after 5-fluorouracil chemotherapy and its possible relationship to dihydropyrimidine dehydrogenase deficiency: a case report and review of the literature. (15700854)
2004
21
Severe toxicity after treatment with capecitabine and fluorouracil due to partial dihydropyrimidine dehydrogenase deficiency]. (15083629)
2004
22
5FU and oxaliplatin-containing chemotherapy in two dihydropyrimidine dehydrogenase-deficient patients. (15274386)
2004
23
Dihydropyrimidine dehydrogenase deficiency and acute neurological presentation. (12971429)
2003
24
Diagnosis of dihydropyrimidine dehydrogenase deficiency in a neonate with thymine-uraciluria. (12668826)
2003
25
Pharmacogenetic and clinical aspects of dihydropyrimidine dehydrogenase deficiency. (12542909)
2003
26
Rapid gas chromatographic-mass spectrometric diagnosis of dihydropyrimidine dehydrogenase deficiency and dihydropyrimidinase deficiency. (12829003)
2003
27
A high-throughput denaturing high-performance liquid chromatography method for the identification of variant alleles associated with dihydropyrimidine dehydrogenase deficiency. (12069415)
2002
28
The effect of dihydropyrimidine dehydrogenase deficiency on outcomes with fluorouracil. (12140902)
2002
29
Increased risk of grade IV neutropenia after administration of 5-fluorouracil due to a dihydropyrimidine dehydrogenase deficiency: high prevalence of the IVS14+1g>a mutation. (12209976)
2002
30
Pitfalls in the diagnosis of patients with a partial dihydropyrimidine dehydrogenase deficiency. (10620566)
2000
31
Dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil associated toxicity. (11783494)
2000
32
Leukaemic expression of anaplastic large cell lymphoma with 46,XX,ins(2;5)(p23;q15q35) in a child with dihydropyrimidine dehydrogenase deficiency. (10764168)
2000
33
Clinical and biochemical abnormalities in a patient with dihydropyrimidine dehydrogenase deficiency due to homozygosity for the C29R mutation. (10234617)
1999
34
Life-threatening toxicity in a dihydropyrimidine dehydrogenase-deficient patient after treatment with topical 5-fluorouracil. (10473079)
1999
35
Prolonged severe 5-fluorouracil-associated neurotoxicity in a patient with dihydropyrimidine dehydrogenase deficiency. (10099659)
1999
36
Clinical variability in three Danish patients with dihydropyrimidine dehydrogenase deficiency all homozygous for the same mutation. (9686373)
1998
37
Dihydropyrimidine dehydrogenase deficiency. Identification of two novel mutations and expression of missense mutations in E. coli. (9598088)
1998
38
Dihydropyrimidine dehydrogenase deficiency: a potential etiology for 5-fluorouracil-induced neurotoxicity. (9250572)
1997
39
Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity. (8698850)
1996
40
A point mutation in an invariant splice donor site leads to exon skipping in two unrelated Dutch patients with dihydropyrimidine dehydrogenase deficiency. (8892022)
1996
41
Severe 5-fluorouracil toxicity possibly secondary to dihydropyrimidine dehydrogenase deficiency in a breast cancer patient with osteogenesis imperfecta. (8664058)
1996
42
Diagnostic analysis, clinical importance and molecular basis of dihydropyrimidine dehydrogenase deficiency. (7491709)
1995
43
Severe fluorouracil toxicity in a patient with dihydropyrimidine dehydrogenase deficiency. (8411234)
1993
44
Dihydropyrimidine dehydrogenase deficiency in a Hutterite newborn. (1781388)
1991
45
The first prenatal diagnosis of dihydropyrimidine dehydrogenase deficiency. (2029924)
1991
46
A new case of dihydropyrimidine dehydrogenase deficiency. (2109146)
1990
47
A screening method for dihydropyrimidine dehydrogenase deficiency with colorimetric detection of urinary uracil. (2624179)
1989
48
Dihydropyrimidine dehydrogenase deficiency. Neurological aspects. (3572451)
1987
49
Dihydropyrimidine dehydrogenase deficiency--a further case. (3930855)
1985
50
Dihydropyrimidine dehydrogenase deficiency leading to thymine-uraciluria. An inborn error of pyrimidine metabolism. (6488556)
1984

Variations for Dihydropyrimidine Dehydrogenase Deficiency

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UniProtKB/Swiss-Prot genetic disease variations for Dihydropyrimidine Dehydrogenase Deficiency:

62
id Symbol AA change Variation ID SNP ID
1DPYDp.Cys29ArgVAR_005173rs1801265
2DPYDp.Arg235TrpVAR_005174rs1801266
3DPYDp.Arg886HisVAR_005177rs1801267

Clinvar genetic disease variations for Dihydropyrimidine Dehydrogenase Deficiency:

6
id Gene Variation Type Significance SNP ID Assembly Location
1DPYDNM_000110.3(DPYD): c.1905+1G> Asingle nucleotide variantPathogenicrs3918290GRCh37Chr 1, 97915614: 97915614
2DPYDDPYD, 4-BP DEL, 296TCATdeletionPathogenic
3DPYDNM_000110.3(DPYD): c.85T> C (p.Cys29Arg)single nucleotide variantPathogenicrs1801265GRCh37Chr 1, 98348885: 98348885
4DPYDDPYD, 1-BP DEL, 1897CdeletionPathogenic
5NM_000110.3(DPYD): c.2657G> A (p.Arg886His)single nucleotide variantPathogenicrs1801267GRCh37Chr 1, 97564154: 97564154

Expression for genes affiliated with Dihydropyrimidine Dehydrogenase Deficiency

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Search GEO for disease gene expression data for Dihydropyrimidine Dehydrogenase Deficiency.

Pathways for genes affiliated with Dihydropyrimidine Dehydrogenase Deficiency

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Pathways related to Dihydropyrimidine Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
9.5DPYD, TYMS
2
Show member pathways
phenylethylamine degradation I36
9.4DPYS, DPYD
3
Show member pathways
9.4DPYS, DPYD
49.4DPYS, DPYD
5
Show member pathways
thymine degradation36
pyrimidine deoxyribonucleosides degradation36
uracil degradation I (reductive)36
pyrimidine ribonucleosides degradation36
9.4DPYD, DPYS
6
Show member pathways
9.4DPYS, DPYD
7
Show member pathways
8.9DPYS, DPYD, TYMS
8
Show member pathways
UTP and CTP dephosphorylation II36
ATP ITP metabolism58
purine deoxyribonucleosides salvage36
8.1TYMS, ADSL, DPYD, DPYS
9
Show member pathways
8.1TYMS, ADSL, DPYD, DPYS
10
Show member pathways
purine deoxyribonucleosides degradation36
purine nucleotides degradation36
adenine and adenosine salvage II36
adenine and adenosine salvage III36
oxidized GTP and dGTP detoxification36
urate biosynthesis/inosine 5-phosphate degradation36
adenine and adenosine salvage I36
purine ribonucleosides degradation to ribose-1-phosphate36
inosine-5-phosphate biosynthesis36
guanosine nucleotides degradation36
guanine and guanosine salvage36
adenosine nucleotides degradation36
5-aminoimidazole ribonucleotide biosynthesis36
8.1DPYS, DPYD, ADSL, TYMS

Compounds for genes affiliated with Dihydropyrimidine Dehydrogenase Deficiency

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Compounds related to Dihydropyrimidine Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

(show all 47)
idCompoundScoreTop Affiliating Genes
1pyrimidine analogues499.9TYMS, DPYD
2tegafur-uracil439.9TYMS, DPYD
3eniluracil439.9TYMS, DPYD
42-deoxyuridine-5-monophosphate439.9TYMS, DPYD
5bvdu439.9DPYD, TYMS
65-fluoro-2-deoxyuridine-5-monophosphate439.9DPYD, TYMS
7tegafur43 4910.9TYMS, DPYD
8idurd439.9TYMS, DPYD
95-deoxy-5-fluorouridine439.9TYMS, DPYD
10orotic acid43 24 1211.9DPYD, TYMS
11tomudex439.9TYMS, DPYD
12capecitabine43 49 1211.9TYMS, DPYD
13thiopurine439.9DPYD, TYMS
14deoxyuridine43 2410.9TYMS, DPYD
15fudr439.8DPYD, TYMS
16Dihydrothymine249.8DPYD, DPYS
17taxane439.8DPYD, TYMS
18sn 3843 5910.8TYMS, DPYD
195,6-dihydrothymine439.8DPYD, DPYS
20cetuximab43 49 1211.8DPYD, TYMS
21fluorouracil49 1210.8TYMS, DPYD
22dihydrouracil43 2410.8DPYS, DPYD
23leucovorin43 49 1211.8TYMS, DPYD
24oxaliplatin43 49 1211.8DPYD, TYMS
25irinotecan43 49 1211.7TYMS, DPYD
26thymine43 2410.7DPYD, DPYS
27gemcitabine43 49 1211.7DPYD, TYMS
28mitomycin c439.7DPYD, TYMS
29adenylosuccinate439.6DPYD, ADSL
30thymidylate439.6DPYD, TYMS
31prpp439.6ADSL, DPYD
32camptothecin43 59 1211.5TYMS, DPYD
33methotrexate49 43 1211.5DPYD, TYMS
345-methylthioadenosine439.5TYMS, ADSL
35xanthine43 2410.4DPYD, ADSL
36aicar43 24 1211.4ADSL, TYMS
37hypoxanthine43 24 1211.4ADSL, TYMS
38docetaxel43 49 59 1212.4DPYD, TYMS
39ornithine43 2410.3ADSL, DPYD
40nucleoside439.3DPYD, ADSL
41pyrimidine43 2410.3DPYS, DPYD, TYMS
425fluorouracil439.3DPYS, DPYD, TYMS
43folate439.2DPYD, TYMS
44molybdenum43 2410.0DPYS, DPYD, ADSL
45purine nucleoside439.0ADSL, DPYD, DPYS
46purine43 249.5DPYS, DPYD, ADSL, TYMS
47thymidine43 249.5TYMS, ADSL, DPYD, DPYS

GO Terms for genes affiliated with Dihydropyrimidine Dehydrogenase Deficiency

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Cellular components related to Dihydropyrimidine Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1cytosolGO:00058298.1DPYS, DPYD, ADSL, TYMS

Biological processes related to Dihydropyrimidine Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

(show all 7)
idNameGO IDScoreTop Affiliating Genes
1uracil catabolic processGO:00062129.5DPYS, DPYD
2thymine catabolic processGO:00062109.4DPYD, DPYS
3pyrimidine nucleobase catabolic processGO:00062089.3DPYS, DPYD
4pyrimidine nucleoside catabolic processGO:00461359.1DPYS, DPYD
5pyrimidine nucleobase metabolic processGO:00062069.0TYMS, DPYD, DPYS
6nucleobase-containing small molecule metabolic processGO:00550868.2DPYS, DPYD, ADSL, TYMS
7small molecule metabolic processGO:00442818.1DPYS, DPYD, ADSL, TYMS

Products for genes affiliated with Dihydropyrimidine Dehydrogenase Deficiency

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Sources for Dihydropyrimidine Dehydrogenase Deficiency

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
33MeSH
34MESH via Orphanet
35MGI
38NCIt
39NDF-RT
42NINDS
43Novoseek
45OMIM
46OMIM via Orphanet
50PubMed
51QIAGEN
56SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet