MCID: DHY011
MIFTS: 39

Dihydropyrimidinase Deficiency

Categories: Genetic diseases, Rare diseases, Metabolic diseases

Aliases & Classifications for Dihydropyrimidinase Deficiency

MalaCards integrated aliases for Dihydropyrimidinase Deficiency:

Name: Dihydropyrimidinase Deficiency 57 53 25 59 75 37 29 6 40 73
Dihydropyrimidinuria 57 53 25 59 13 73
Dpys Deficiency 57 53 25 75
Dph Deficiency 57 53 25 75
Dpysd 57 75
Dihydropyrimidinuria Due to Dpys Deficiency 75
Dihydrouracil Amidohydrolase Deficiency 25
Dihydropyrimidinase 13

Characteristics:

Orphanet epidemiological data:

59
dihydropyrimidinuria
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM:

57
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
dihydropyrimidinase deficiency:
Onset and clinical course phenotypic variability
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Inborn errors of metabolism


Summaries for Dihydropyrimidinase Deficiency

NIH Rare Diseases : 53 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.

MalaCards based summary : Dihydropyrimidinase Deficiency, also known as dihydropyrimidinuria, is related to dihydropyrimidine dehydrogenase deficiency and neuroblastoma. An important gene associated with Dihydropyrimidinase Deficiency is DPYS (Dihydropyrimidinase), and among its related pathways/superpathways are Pyrimidine metabolism and Drug metabolism - other enzymes. Affiliated tissues include testes, and related phenotypes are delayed speech and language development and intellectual disability

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 : 57 DPYS deficiency is an autosomal recessive disease characterized by the presence of dihydropyrimidinuria. The clinical phenotype is highly variable, ranging from early infantile onset of severe neurologic involvement, dysmorphic features, and feeding problems to late onset of mild intellectual disability and even asymptomatic individuals. Patients with a complete or partial deficiency have an increased risk of developing severe toxicity after administration of the anticancer drug 5-fluorouracil (5-FU) (summary by Nakajima et al., 2017). See also dihydropyrimidine dehydrogenase deficiency (274270), a similar disorder. (222748)

UniProtKB/Swiss-Prot : 75 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 Dihydropyrimidinase Deficiency

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

(show all 13)
# Related Disease Score Top Affiliating Genes
1 dihydropyrimidine dehydrogenase deficiency 28.8 DPYD DPYS
2 neuroblastoma 10.5
3 schizophrenia 10.2
4 polycystic kidney disease 10.1
5 alzheimer disease 10.0
6 down syndrome 10.0
7 chromophobe renal cell carcinoma 9.9
8 endometriosis 9.9
9 hepatocellular carcinoma 9.8
10 gastric cancer 9.8
11 pyrimidine metabolic disorder 9.8 DPYD DPYS
12 beta-ureidopropionase deficiency 9.7 DPYD DPYS
13 purine-pyrimidine metabolic disorder 9.6 DPYD DPYS

Graphical network of the top 20 diseases related to Dihydropyrimidinase Deficiency:



Diseases related to Dihydropyrimidinase Deficiency

Symptoms & Phenotypes for Dihydropyrimidinase Deficiency

Symptoms via clinical synopsis from OMIM:

57
Growth Other:
growth retardation (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
Head And Neck Head:
plagiocephaly (1 patient)

Abdomen Gastrointestinal:
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 Dihydropyrimidinase Deficiency:

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

GenomeRNAi Phenotypes related to Dihydropyrimidinase Deficiency according to GeneCards Suite gene sharing:

26 (show all 11)
# 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 Dihydropyrimidinase Deficiency

Search Clinical Trials , NIH Clinical Center for Dihydropyrimidinase Deficiency

Genetic Tests for Dihydropyrimidinase Deficiency

Genetic tests related to Dihydropyrimidinase Deficiency:

# Genetic test Affiliating Genes
1 Dihydropyrimidinase Deficiency 29 DPYS

Anatomical Context for Dihydropyrimidinase Deficiency

MalaCards organs/tissues related to Dihydropyrimidinase Deficiency:

41
Testes

Publications for Dihydropyrimidinase Deficiency

Articles related to Dihydropyrimidinase Deficiency:

(show all 15)
# Title Authors Year
1
Dihydropyrimidinase deficiency in four East Asian patients due to novel and rare DPYS mutations affecting protein structural integrity and catalytic activity. ( 29054612 )
2017
2
Diagnosis of dihydropyrimidinase deficiency in a Chinese boy with dihydropyrimidinuria. ( 23732435 )
2013
3
Dihydropyrimidinase deficiency: the first feline case of dihydropyrimidinuria with clinical and molecular findings. ( 23430934 )
2012
4
Dihydropyrimidinase deficiency: Phenotype, genotype and structural consequences in 17 patients. ( 20362666 )
2010
5
Beta-alanine and beta-aminoisobutyric acid levels in two siblings with dihydropyrimidinase deficiency. ( 18600547 )
2008
6
Clinical, biochemical and genetic findings in two siblings with a dihydropyrimidinase deficiency. ( 17383919 )
2007
7
Rapid gas chromatographic-mass spectrometric diagnosis of dihydropyrimidine dehydrogenase deficiency and dihydropyrimidinase deficiency. ( 12829003 )
2003
8
Dihydropyrimidinase deficiency and severe 5-fluorouracil toxicity. ( 14555507 )
2003
9
Clinical and biochemical aspects of dihydropyrimidinase deficiency. ( 9598044 )
1998
10
[Dihydropyrimidinase deficiency (dihydropyrimidinuria)]. ( 9590033 )
1998
11
Dihydropyrimidinase deficiency: structural organization, chromosomal localization, and mutation analysis of the human dihydropyrimidinase gene. ( 9718352 )
1998
12
Dihydropyrimidinase deficiency: confirmation of the enzyme defect in dihydropyrimidinuria. ( 9266350 )
1997
13
Dihydropyrimidinase deficiency, a progressive neurological disorder? ( 9208410 )
1997
14
Dihydropyrimidinase deficiency and congenital microvillous atrophy: coincidence or genetic relation? ( 9323563 )
1997
15
Dihydropyrimidinase deficiency presenting in infancy with severe developmental delay. ( 7541877 )
1993

Variations for Dihydropyrimidinase Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Dihydropyrimidinase Deficiency:

75
# 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 Dihydropyrimidinase Deficiency:

6
(show all 40)
# 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.1001A> G (p.Gln334Arg) single nucleotide variant Pathogenic rs121964923 GRCh38 Chromosome 8, 104428071: 104428071
3 DPYS NM_001385.2(DPYS): c.1303G> A (p.Gly435Arg) single nucleotide variant Pathogenic rs267606773 GRCh37 Chromosome 8, 105405152: 105405152
4 DPYS NM_001385.2(DPYS): c.1303G> A (p.Gly435Arg) single nucleotide variant Pathogenic rs267606773 GRCh38 Chromosome 8, 104392924: 104392924
5 DPYS NM_001385.2(DPYS): c.1078T> C (p.Trp360Arg) single nucleotide variant Pathogenic rs121964924 GRCh37 Chromosome 8, 105440222: 105440222
6 DPYS NM_001385.2(DPYS): c.1078T> C (p.Trp360Arg) single nucleotide variant Pathogenic rs121964924 GRCh38 Chromosome 8, 104427994: 104427994
7 DPYS NM_001385.2(DPYS): c.1235G> T (p.Arg412Met) single nucleotide variant Pathogenic rs267606774 GRCh37 Chromosome 8, 105436475: 105436475
8 DPYS NM_001385.2(DPYS): c.1235G> T (p.Arg412Met) single nucleotide variant Pathogenic rs267606774 GRCh38 Chromosome 8, 104424247: 104424247
9 DPYS NM_001385.2(DPYS): c.424-1G> A single nucleotide variant Pathogenic rs879851088 GRCh37 Chromosome 8, 105459732: 105459732
10 DPYS NM_001385.2(DPYS): c.424-1G> A single nucleotide variant Pathogenic rs879851088 GRCh38 Chromosome 8, 104447504: 104447504
11 DPYS NM_001385.2(DPYS): c.817A> G (p.Ile273Val) single nucleotide variant Uncertain significance rs201924473 GRCh37 Chromosome 8, 105441906: 105441906
12 DPYS NM_001385.2(DPYS): c.817A> G (p.Ile273Val) single nucleotide variant Uncertain significance rs201924473 GRCh38 Chromosome 8, 104429678: 104429678
13 DPYS NM_001385.2(DPYS): c.*351dupA duplication Likely benign rs143004875 GRCh37 Chromosome 8, 105391735: 105391735
14 DPYS NM_001385.2(DPYS): c.*351dupA duplication Likely benign rs143004875 GRCh38 Chromosome 8, 104379507: 104379507
15 DPYS NM_001385.2(DPYS): c.*344T> A single nucleotide variant Likely benign rs73699419 GRCh37 Chromosome 8, 105391742: 105391742
16 DPYS NM_001385.2(DPYS): c.*344T> A single nucleotide variant Likely benign rs73699419 GRCh38 Chromosome 8, 104379514: 104379514
17 DPYS NM_001385.2(DPYS): c.793+10G> T single nucleotide variant Uncertain significance rs200495434 GRCh37 Chromosome 8, 105456466: 105456466
18 DPYS NM_001385.2(DPYS): c.793+10G> T single nucleotide variant Uncertain significance rs200495434 GRCh38 Chromosome 8, 104444238: 104444238
19 DPYS NM_001385.2(DPYS): c.603+5G> A single nucleotide variant Uncertain significance rs377073619 GRCh37 Chromosome 8, 105459547: 105459547
20 DPYS NM_001385.2(DPYS): c.603+5G> A single nucleotide variant Uncertain significance rs377073619 GRCh38 Chromosome 8, 104447319: 104447319
21 DPYS NM_001385.2(DPYS): c.*205G> A single nucleotide variant Uncertain significance rs146388435 GRCh37 Chromosome 8, 105391881: 105391881
22 DPYS NM_001385.2(DPYS): c.*205G> A single nucleotide variant Uncertain significance rs146388435 GRCh38 Chromosome 8, 104379653: 104379653
23 DPYS NM_001385.2(DPYS): c.*200T> C single nucleotide variant Uncertain significance rs577662244 GRCh37 Chromosome 8, 105391886: 105391886
24 DPYS NM_001385.2(DPYS): c.*200T> C single nucleotide variant Uncertain significance rs577662244 GRCh38 Chromosome 8, 104379658: 104379658
25 DPYS NM_001385.2(DPYS): c.*70A> T single nucleotide variant Uncertain significance rs781457040 GRCh37 Chromosome 8, 105392016: 105392016
26 DPYS NM_001385.2(DPYS): c.*70A> T single nucleotide variant Uncertain significance rs781457040 GRCh38 Chromosome 8, 104379788: 104379788
27 DPYS NM_001385.2(DPYS): c.1350C> T (p.Ala450=) single nucleotide variant Likely benign rs75490773 GRCh37 Chromosome 8, 105405105: 105405105
28 DPYS NM_001385.2(DPYS): c.1350C> T (p.Ala450=) single nucleotide variant Likely benign rs75490773 GRCh38 Chromosome 8, 104392877: 104392877
29 DPYS NM_001385.2(DPYS): c.856A> T (p.Asn286Tyr) single nucleotide variant Uncertain significance rs886062588 GRCh37 Chromosome 8, 105441867: 105441867
30 DPYS NM_001385.2(DPYS): c.856A> T (p.Asn286Tyr) single nucleotide variant Uncertain significance rs886062588 GRCh38 Chromosome 8, 104429639: 104429639
31 DPYS NM_001385.2(DPYS): c.*408A> G single nucleotide variant Uncertain significance rs555961371 GRCh37 Chromosome 8, 105391678: 105391678
32 DPYS NM_001385.2(DPYS): c.*408A> G single nucleotide variant Uncertain significance rs555961371 GRCh38 Chromosome 8, 104379450: 104379450
33 DPYS NM_001385.2(DPYS): c.17G> A (p.Arg6Gln) single nucleotide variant Likely benign rs199618701 GRCh37 Chromosome 8, 105479132: 105479132
34 DPYS NM_001385.2(DPYS): c.17G> A (p.Arg6Gln) single nucleotide variant Likely benign rs199618701 GRCh38 Chromosome 8, 104466904: 104466904
35 DPYS NM_001385.2(DPYS): c.*166_*169delGTCT deletion Uncertain significance rs539754034 GRCh37 Chromosome 8, 105391917: 105391920
36 DPYS NM_001385.2(DPYS): c.*166_*169delGTCT deletion Uncertain significance rs539754034 GRCh38 Chromosome 8, 104379689: 104379692
37 DPYS NM_001385.2(DPYS): c.672A> G (p.Ala224=) single nucleotide variant Likely benign rs7825427 GRCh37 Chromosome 8, 105456597: 105456597
38 DPYS NM_001385.2(DPYS): c.672A> G (p.Ala224=) single nucleotide variant Likely benign rs7825427 GRCh38 Chromosome 8, 104444369: 104444369
39 DPYS NM_001385.2(DPYS): c.131G> T (p.Gly44Val) single nucleotide variant Uncertain significance rs367711099 GRCh37 Chromosome 8, 105479018: 105479018
40 DPYS NM_001385.2(DPYS): c.131G> T (p.Gly44Val) single nucleotide variant Uncertain significance rs367711099 GRCh38 Chromosome 8, 104466790: 104466790

Expression for Dihydropyrimidinase Deficiency

Search GEO for disease gene expression data for Dihydropyrimidinase Deficiency.

Pathways for Dihydropyrimidinase Deficiency

Pathways related to Dihydropyrimidinase Deficiency according to KEGG:

37
# Name Kegg Source Accession
1 Pyrimidine metabolism hsa00240
2 Drug metabolism - other enzymes hsa00983

Pathways related to Dihydropyrimidinase Deficiency according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.94 DPYD DPYS
2
Show member pathways
11.66 DPYD DPYS
3
Show member pathways
11.39 DPYD DPYS
4
Show member pathways
10.69 DPYD DPYS
5 10.23 DPYD DPYS
6
Show member pathways
9.88 DPYD DPYS

GO Terms for Dihydropyrimidinase Deficiency

Biological processes related to Dihydropyrimidinase Deficiency according to GeneCards Suite gene sharing:

# 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 Dihydropyrimidinase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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