MCID: DHY002
MIFTS: 55

Dihydropyrimidine Dehydrogenase Deficiency malady

Genetic diseases, Rare diseases, Metabolic diseases categories
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Summaries for Dihydropyrimidine Dehydrogenase Deficiency

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NIH Rare Diseases:42 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 5-fluorouracil toxicity and colorectal cancer, and has symptoms including An important gene associated with Dihydropyrimidine Dehydrogenase Deficiency is DPYD (dihydropyrimidine dehydrogenase), and among its related pathways are Pyrimidine metabolism and Glucuronidation. The compounds Dihydrothymine and 5,6-dihydrothymine have been mentioned in the context of this disorder. Affiliated tissues include testes, bone marrow and bone.

Disease Ontology:8 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.

Wikipedia:65 Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) is an autosomal recessivemetabolic disorder... more...

Description from OMIM:46 274270

Aliases & Classifications for Dihydropyrimidine Dehydrogenase Deficiency

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Sources:
8Disease Ontology, 42NIH Rare Diseases, 21Genetics Home Reference, 46OMIM, 10DISEASES, 48Orphanet, 62UMLS, 9diseasecard, 20GeneTests, 22GTR, 57SNOMED-CT, 39NCIt, 34MeSH, 35MESH via Orphanet, 26ICD10 via Orphanet, 63UMLS via Orphanet
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Dihydropyrimidine Dehydrogenase Deficiency, Aliases & Descriptions:

Name: Dihydropyrimidine Dehydrogenase Deficiency 8 42 21 46 10 48 62
Dihydropyrimidine Dehydrogenase 9 20 22
Hereditary Thymine-Uraciluria 42 21
Familial Pyrimidinemia 42 48
Familial Pyrimidemia 21 62
 
Dihydropyrimidinuria 21 62
Thymine-Uracilurea 8 62
Dpd Deficiency 42 21
Dihydrouracil Dehydrogenase Deficiency 8
Familial Pyrimidinaemia 8


Classifications:



External Ids:

Disease Ontology8 DOID:14218
NCIt39 C3964
OMIM46 274270
MeSH34 D054067
SNOMED-CT57 238016000, 77365006
MESH via Orphanet35 D054067
ICD10 via Orphanet26 E79.8
UMLS via Orphanet63 C1959620

Related Diseases for Dihydropyrimidine Dehydrogenase Deficiency

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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:

32
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 77)
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:

64
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 Name 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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Expression patterns in normal tissues for genes affiliated with Dihydropyrimidine Dehydrogenase Deficiency

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Pathways for genes affiliated with Dihydropyrimidine Dehydrogenase Deficiency

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Pathways related to Dihydropyrimidine Dehydrogenase Deficiency according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
9.3DPYS, DPYD
2
Show member pathways
9.3DPYD, DPYS
3
Show member pathways
phenylethylamine degradation I37
9.3DPYS, DPYD
49.3DPYD, DPYS
5
Show member pathways
9.3DPYS, DPYD
6
Show member pathways
thymine degradation37
pyrimidine deoxyribonucleosides degradation37
uracil degradation I (reductive)37
pyrimidine ribonucleosides degradation37
9.3DPYD, DPYS
7
Show member pathways
8.5DPYS, DPYD, ADSL
8
Show member pathways
UTP and CTP dephosphorylation II37
ATP ITP metabolism60
purine deoxyribonucleosides salvage37
8.5DPYS, DPYD, ADSL
9
Show member pathways
purine deoxyribonucleosides degradation37
purine nucleotides degradation37
adenine and adenosine salvage II37
adenine and adenosine salvage III37
oxidized GTP and dGTP detoxification37
urate biosynthesis/inosine 5-phosphate degradation37
adenine and adenosine salvage I37
purine ribonucleosides degradation to ribose-1-phosphate37
inosine-5-phosphate biosynthesis37
guanosine nucleotides degradation37
guanine and guanosine salvage37
adenosine nucleotides degradation37
5-aminoimidazole ribonucleotide biosynthesis37
8.5DPYS, DPYD, ADSL

Compounds for genes affiliated with Dihydropyrimidine Dehydrogenase Deficiency

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Sources:
24HMDB, 44Novoseek
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Compounds related to Dihydropyrimidine Dehydrogenase Deficiency according to GeneCards/GeneDecks:

(show all 15)
idCompoundScoreTop Affiliating Genes
1Dihydrothymine249.6DPYS, DPYD
25,6-dihydrothymine449.6DPYD, DPYS
3dihydrouracil44 2410.6DPYS, DPYD
4thymine44 2410.5DPYS, DPYD
5adenylosuccinate449.3DPYD, ADSL
6pyrimidine44 2410.3DPYD, DPYS
75fluorouracil449.3DPYS, DPYD
8prpp449.3ADSL, DPYD
9xanthine44 2410.2DPYD, ADSL
10ornithine44 2410.0DPYD, ADSL
11nucleoside448.8DPYD, ADSL
12molybdenum44 249.8DPYS, DPYD, ADSL
13purine nucleoside448.8DPYS, DPYD, ADSL
14purine44 249.8DPYS, DPYD, ADSL
15thymidine44 249.6DPYS, DPYD, ADSL

GO Terms for genes affiliated with Dihydropyrimidine Dehydrogenase Deficiency

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Biological processes related to Dihydropyrimidine Dehydrogenase Deficiency according to GeneCards/GeneDecks:

(show all 7)
idNameGO IDScoreTop Affiliating Genes
1uracil catabolic processGO:0062129.5DPYS, DPYD
2thymine catabolic processGO:0062109.4DPYS, DPYD
3pyrimidine nucleobase catabolic processGO:0062089.3DPYD, DPYS
4pyrimidine nucleoside catabolic processGO:0461359.2DPYS, DPYD
5pyrimidine nucleobase metabolic processGO:0062069.0DPYS, DPYD
6nucleobase-containing small molecule metabolic processGO:0550868.6DPYS, DPYD, ADSL
7small molecule metabolic processGO:0442818.5DPYS, DPYD, ADSL

Products for genes affiliated with Dihydropyrimidine Dehydrogenase Deficiency

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  • Antibodies
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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
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet