Dihydropyrimidine Dehydrogenase Deficiency malady

NIH Rare Diseases: 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.³⁰

MalaCards: Dihydropyrimidine Dehydrogenase Deficiency, also known as hereditary thymine-uraciluria, is related to 5-fluorouracil toxicity and dihydropyrimidinase deficiency. An important gene associated with Dihydropyrimidine Dehydrogenase Deficiency is DPYD (dihydropyrimidine dehydrogenase), and among its related pathways are Beta-alanine metabolism and Beta-alanine metabolism. The compounds adenylosuccinate and prpp have been mentioned in the context of this disorder. Affiliated tissues include breast.

Disease Ontology: 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.⁶

Genetics Home Reference: 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.¹⁷

Wikipedia: Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) is an autosomal recessivemetabolic disorder...⁴⁴ more...

OMIM: 274270

Aliases & Descriptions:

dihydropyrimidine dehydrogenase deficiency 6 30 17 8 33 43 hereditary thymine-uraciluria 30 16 17 familial pyrimidinemia 30 16 43 dpd deficiency 30 16 17 dihydropyrimidine dehydrogenase deficiency (disorder) 6 16 dihydrouracil dehydrogenase (nadp^+^) deficiency 43

dihydrouracil dehydrogenase deficiency 6 dihydropyrimidinase deficiency 43 familial pyrimidinaemia 6 dihydropyrimidinuria 17 familial pyrimidemia 17 thymine-uracilurea 6

Diseases related to dihydropyrimidine dehydrogenase deficiency by text searches and GeneDecks gene sharing:

(show all 16)

id	Related Disease	Score	Top Affiliating Genes
1	5-fluorouracil toxicity	31.4	DPYD, DPYS
2	dihydropyrimidinase deficiency	29.4	DPYD, DPYS
3	dihydropyrimidinuria	29.2	DPYD, DPYS
4	purine-pyrimidine metabolic disorder	12.8	DPYD, ADSL
5	beta-ureidopropionase deficiency	12.6	DPYD, DPYS
6	aicardi-goutieres syndrome	12.5	DPYD, ADSL
7	recessive developmental delay, small stature, microcephaly and brain calcifications	12.2	ADSL, DPYS, DPYD
8	convulsions	12.1	DPYD, DPYS
9	sensorineural hearing loss	12.1	GPSM2, COL11A1
10	hearing loss	11.7	DPYD, COL11A1, GPSM2
11	breast cancer	7.0
12	colorectal cancer	7.0
13	neutropenia	7.0
14	osteogenesis imperfecta	7.0
15	thymine-uraciluria	7.0
16	gastric cancer	6.2

Clinical features from OMIM: 274270

Approved drugs:

Drug clinical trials:

Genetic tests related to dihydropyrimidine dehydrogenase deficiency:

id	Genetic test	Affiliating Genes
1	Dihydropyrimidine Dehydrogenase Deficiency clinical/research	DPYD

MalaCards organs/tissues related to dihydropyrimidine dehydrogenase deficiency:

²²

Articles related to dihydropyrimidine dehydrogenase deficiency:

(show all 35)

id	Title	Authors	Year	Affiliating Genes
1	Dihydropyrimidine dehydrogenase deficiency and toxic ity to fluoropyrimidine (20146975)	Boisdron-Celle M.... Gamelin E.	2010	DPYD
2	Dihydropyrimidine dehydrogenase deficiency caused by a novel genomic deletion c.505_513del of DPYD. (20544545)	Van Kuilenburg A.B.... Hennekam R.C.	2010	DPYD
3	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)	Van Kuilenburg A.B.... Rubio-Gozalbo M.E.	2009	DPYD, COL11A1
4	The dihydrouracil/uracil ratio in plasma, clinical an d genetic analysis for screening of dihydropyrimidine dehydrogenase deficiency in colorectal cancer patients treated with 5-fluorouracil. (18619742)	Ben Fredj R.... Saguem S.	2009	DPYD
5	Dihydropyrimidine dehydrogenase deficiency presenting with psychomotor retardation in the first Polish patient. (19081848)	Mazur A.... Van Kuilenburg A.B.	2008	DPYD
6	Detection of dihydropyrimidine dehydrogenase deficiency before treatment by fluoropyrimidines (17582309)	Gamelin E.... Morel A.	2007	DPYD
7	A pivotal role for beta-aminoisobutyric acid and oxidative stress in dihydropyrimidine dehydrogenase deficiency? (17065072)	Van Kuilenburg A.B.... Van Gennip A.H.	2006	DPYD
8	Increased prevalence of dihydropyrimidine dehydrogenase deficiency in African-Americans compared with Caucasians. (17000684)	Mattison L.K.... Diasio R.B.	2006	DPYD
9	Is capecitabine safe in patients with gastrointestina l cancer and dihydropyrimidine dehydrogenase deficiency? (16512996)	Saif M.W.... Diasio R.	2006	DPYD
10	Profiling dihydropyrimidine dehydrogenase deficiency in patients with cancer undergoing 5-fluorouracil/capecitabine therapy. (17241513)	Mercier C.... Ciccolini J.	2006	DPYD
11	Unpredicted severe toxicity after 5-fluorouracil treatment due to dihydropyrimidine dehydrogenase deficiency. (16646564)	Baek J.H.... Lee K.B.	2006	DPYD
12	Dihydropyrimidine dehydrogenase deficiency in an Indian population. (16421754)	Saif M.W.... Diasio R.B.	2006	DPYD
13	Methylation of the DPYD promoter: an alternative mechanism for dihydropyrimidine dehydrogenase deficiency in cancer patients. (16361556)	Ezzeldin H.H.... Diasio R.B.	2005	DPYD
14	Dihydropyrimidine dehydrogenase deficiency presenting at birth. (16151913)	Al-Sanna'a N.A.... Van Gennip A.H.	2005	DPYD
15	Rapid identification of dihydropyrimidine dehydrogenase deficiency by using a novel 2-13C-uracil breath test. (15102667)	Mattison L.K.... Diasio R.B.	2004	DPYD
16	New insights in dihydropyrimidine dehydrogenase deficiency: a pivotal role for beta-aminoisobutyric acid? (14705962)	Van Kuilenburg A.B.... Van Gennip A.H.	2004	DPYD
17	Severe toxicity after treatment with capecitabine an d fluorouracil due to partial dihydropyrimidine dehydrogenase deficiency (15083629)	Hooiveld E.A.... Westermann A.M.	2004	DPYD
18	Head imaging abnormalities in dihydropyrimidine dehydrogenase deficiency. (15303009)	Enns G.M.... Van Gennip A.H.	2004	DPYD
19	Dihydropyrimidine dehydrogenase deficiency: impact of pharmacogenetics on 5-fluorouracil therapy. (16163233)	Lee A.... Diasio R.	2004	DPYD
20	Pharmacogenetic and clinical aspects of dihydropyrimidine dehydrogenase deficiency. (12542909)	Van Kuilenburg A.B.... Van Gennip A.H.	2003	DPYD
21	Diagnosis of dihydropyrimidine dehydrogenase deficiency in a neonate with thymine-uraciluria. (12668826)	Au K.M.... Chan A.Y.	2003	DPYD
22	Rapid gas chromatographic-mass spectrometric diagnosis of dihydropyrimidine dehydrogenase deficiency and dihydropyrimidinase deficiency. (12829003)	Kuhara T.... Matsumoto I.	2003	DPYD, DPYS
23	Profound dihydropyrimidine dehydrogenase deficiency resulting from a novel compound heterozygote genotype. (11895907)	Johnson M.R.... Diasio R.B.	2002	DPYD
24	The effect of dihydropyrimidine dehydrogenase deficiency on outcomes with fluorouracil. (12140902)	Gardiner S.J.... Robinson B.A.	2002	DPYD
25	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)	Van Kuilenburg A.B.... Van Gennip A.H.	2002	DPYD
26	Pitfalls in the diagnosis of patients with a partial dihydropyrimidine dehydrogenase deficiency. (10620566)	Van Kuilenburg A.B.... Van Gennip A.H.	2000	DPYD
27	Prolonged severe 5-fluorouracil-associated neurotoxic ity in a patient with dihydropyrimidine dehydrogenase deficiency. (10099659)	Shehata N.... Tang S.C.	1999	DPYD
28	Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency. (10071185)	Van Kuilenburg A.B.... Van Gennip A.H.	1999	DPYD
29	Life-threatening toxicity in a dihydropyrimidine dehydrogenase-deficient patient after treatment with topical 5-fluorouracil. (10473079)	Johnson M.R.... Diasio R.B.	1999	DPYD
30	Dihydropyrimidine dehydrogenase deficiency: a pharmacogenetic defect causing severe adverse reactions to 5-fluorouracil-based chemotherapy. (9007910)	Morrison G.B.... Takimoto C.H.	1997	DPYD
31	Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity. (8698850)	Wei X.... Fernandez-Salguero P.	1996	DPYD
32	A point mutation in an invariant splice donor site leads to exon skipping in two unrelated Dutch patients with dihydropyrimidine dehydrogenase deficiency. (8892022)	Vreken P.... Van Gennip A.H.	1996	DPYD
33	Severe 5-fluorouracil toxicity possibly secondary to dihydropyrimidine dehydrogenase deficiency in a breast cancer patient with osteogenesis imperfecta. (8664058)	Beuzeboc P.... Pouillart P.	1996	DPYD
34	Severe 5-fluorouracil toxicity secondary to dihydropyrimidine dehydrogenase deficiency. A potentially more common pharmacogenetic syndrome. (1648430)	Harris B.E.... Diasio R.B.	1991	DPYD
35	A new case of dihydropyrimidine dehydrogenase deficiency. (2109146)	Brockstedt M.... Berger R.	1990	DPYD

Genes related to dihydropyrimidine dehydrogenase deficiency according to GeneCards:

id	Symbol	Description	Score	GeneCards Section Context
1	DPYD	dihydropyrimidine dehydrogenase	11.1	Summaries, Publications
2	LPPR4	lipid phosphate phosphatase-related protein type 4	11.0	Disorders
3	ADSL	adenylosuccinate lyase	11.0
4	DPYS	dihydropyrimidinase	11.0	Publications
5	GPSM2	G-protein signaling modulator 2	11.0
6	COL11A1	collagen, type XI, alpha 1	11.0	Publications

Pathways related to dihydropyrimidine dehydrogenase deficiency according to GeneDecks:

id	Pathway	Score	Top Affiliating Genes
1	Beta-alanine metabolism10	9.6	DPYD, DPYS
2	Beta-alanine metabolism41	9.6	DPYD, DPYS
3	Pantothenate and CoA biosynthesis20	9.6	DPYD, DPYS
4	Pyrimidine metabolism38	9.5	DPYD, DPYS
5	Fluoropyrimidine Pathway, Pharmacokinetics34	9.4	DPYS, DPYD
6	Pyrimidine metabolism20	9.4	DPYD, DPYS
7	beta-Alanine metabolism20	9.3	DPYD, DPYS
8	Drug metabolism - other enzymes20	9.1	DPYD, DPYS

Compounds related to dihydropyrimidine dehydrogenase deficiency according to GeneDecks:

(show all 13)

id	Compound	Score	Top Affiliating Genes
1	adenylosuccinate32	9.7	DPYD, ADSL
2	prpp32	9.7	ADSL, DPYD
3	5,6-dihydrothymine32	9.7	DPYD, DPYS
4	dihydrouracil32 18	10.7	DPYS, DPYD
5	xanthine32 18	10.6	DPYD, ADSL
6	thymine32 18	10.6	DPYD, DPYS
7	nucleoside32	9.5	DPYD, ADSL
8	pyrimidine32 18	10.3	DPYD, DPYS
9	ornithine32 18	10.2	DPYD, ADSL
10	molybdenum32 18	10.2	DPYD, DPYS, ADSL
11	purine nucleoside32	9.2	DPYD, DPYS, ADSL
12	purine32 18	10.1	DPYD, DPYS, ADSL
13	thymidine32 18	9.9	ADSL, DPYS, DPYD

Biological processes related to dihydropyrimidine dehydrogenase deficiency according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	uracil catabolic process	GO:006212	9.6	DPYD, DPYS
2	thymine catabolic process	GO:006210	9.5	DPYD, DPYS
3	pyrimidine nucleobase metabolic process	GO:006206	9.4	DPYD, DPYS
4	pyrimidine nucleobase catabolic process	GO:006208	9.3	DPYD, DPYS
5	pyrimidine nucleoside catabolic process	GO:046135	9.1	DPYD, DPYS
6	nucleobase-containing small molecule metabolic process	GO:055086	8.9	ADSL, DPYS, DPYD