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variants usually show high specificity (i.e., bearing the mutation means that severe toxicity will occur indeed) but very low sensitivity (i.e., not bearing the mutation does not mean that there is no risk for severe toxicities). Alternatively, phenotyping DPD using ex-vivo enzymatic assay or surrogate testing (i.e., monitoring physiological dihydrouracil to uracil ratio in plasma) has been presented as a possible upfront strategy to detect DPD deficiency. 5-FU test dose (i.e., preliminary administration of a small dose of 5-FU with pharmacokinetics evaluation) has been proposed as another possible alternative strategy to secure the use of fluoropyrimidine drugs.
71:
39:
161:(ESMO) guidelines do not âroutinely recommendâ upfront genotyping of DPYD*2A before the administration of 5âFU in metastatic CRC (mCRC) patients. While oncology societies in the United States do not recommend systematic testing. Instead, on April 30, 2020, the European Society for Medical Oncology issued a document recommending
149:
A small number of genetic variants have been repeatedly associated with DPD deficiency, such as IVS14+1G>A mutation in intron 14 coupled with exon 14 deletion (a.k.a. DPYD*2A), 496A>G in exon 6; 2846A>T in exon 22 and T1679G (a.k.a. DPYD*13) in exon 13. Testing patients for these allelic
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132:, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both
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603:
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658:
630:
312:
Mercier C, Ciccolini J (Nov 2006). "Profiling dihydropyrimidine dehydrogenase deficiency in patients with cancer undergoing 5-fluorouracil/capecitabine therapy".
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706:
277:
Lee A, Ezzeldin H, Fourie J, Diasio R (Aug 2004). "Dihydropyrimidine dehydrogenase deficiency: impact of pharmacogenetics on 5-fluorouracil therapy".
187:"Familial deficiency of dihydropyrimidine dehydrogenase: biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity"
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158:
355:
Mercier C, Ciccolini J (Dec 2007). "Severe or lethal toxicities upon capecitabine intake: is DPYD genetic polymorphism the ideal culprit?".
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DPD deficiency is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an
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451:"All You Need to Know About DPYD Genetic Testing for Patients Treated With Fluorouracil and Capecitabine: A Practitioner-Friendly Guide"
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234:
Van
Kuilenburg AB (Mar 2006). "Screening for dihydropyrimidine dehydrogenase deficiency: to do or not to do, that's the question".
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154:
626:
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Innocenti, Federico; Mills, Sarah C.; Sanoff, Hanna; Ciccolini, Joseph; Lenz, Heinz-Josef; Milano, Gerard (2020).
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Although DPYD pre-treatment screening has been proven to improve drug safety for DPYD*2A carriers by the
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120:(Xeloda) could put DPD-deficient patients at risk of experiencing severe or lethal toxicities as well.
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one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.
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drug that is used in the treatment of cancer. Beside 5-FU, widely prescribed oral fluoropyrimidine
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Individuals with this condition may develop life-threatening toxicity following exposure to
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Dihydropyrimidine dehydrogenase deficiency has an autosomal recessive pattern of
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in which there is absent or significantly decreased activity of
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392:"Precision treatment in colorectal cancer: Now and the future"
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Mitochondrial neurogastrointestinal encephalopathy syndrome
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185:Diasio RB, Beavers TL, Carpenter JT (Jan 1988).
279:Clinical Advances in Hematology & Oncology
797:Inborn errors of purine-pyrimidine metabolism
611:
8:
686:Adenine phosphoribosyltransferase deficiency
772:Dihydropyrimidine dehydrogenase deficiency
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707:Purine nucleoside phosphorylase deficiency
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583:Dihydropyrimidine dehydrogenase deficiency
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97:, an enzyme involved in the metabolism of
81:Dihydropyrimidine dehydrogenase deficiency
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22:Dihydropyrimidine dehydrogenase deficiency
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159:European Society for Medical Oncology
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357:Trends in Pharmacological Sciences
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654:Adenylosuccinate lyase deficiency
95:dihydropyrimidine dehydrogenase
702:Adenosine deaminase deficiency
157:, the current (version 2016)
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802:Autosomal recessive disorders
390:Yau, Tung On (October 2019).
631:purineâpyrimidine metabolism
155:Food and Drug Administration
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369:10.1016/j.tips.2007.09.009
314:Clinical Colorectal Cancer
248:10.1080/07357900500524702
45:
36:
326:10.3816/CCC.2006.n.047
736:Pyrimidine metabolism
455:JCO Oncology Practice
677:LeschâNyhan syndrome
236:Cancer Investigation
467:10.1200/OP.20.00553
669:Nucleotide salvage
555:External resources
409:10.1002/jgh3.12153
91:metabolic disorder
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639:Purine metabolism
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16:Medical condition
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461:(12): 793â798.
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363:(12): 597â598.
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504:Classification
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402:(5): 361â369.
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320:(4): 288â296.
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285:(8): 527â532.
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110:5-fluorouracil
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31:DPD deficiency
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681:Hyperuricemia
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591:Rare Diseases
589:'s Office of
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197:(1): 47â51.
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118:capecitabine
114:chemotherapy
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30:
712:Xanthinuria
48:inheritance
27:Other names
791:Categories
765:Catabolism
695:Catabolism
540:DiseasesDB
169:References
112:(5-FU), a
744:Anabolism
647:Anabolism
418:2397-9070
334:1533-0028
291:1543-0790
145:Detection
140:Diagnosis
88:recessive
85:autosomal
56:Specialty
564:Orphanet
485:33197222
436:31633039
396:JGH Open
377:18001850
342:17241513
299:16163233
256:16537192
130:autosome
124:Genetics
534:D054067
476:8462561
427:6788378
264:5746790
221:3335642
103:thymine
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99:uracil
83:is an
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545:29817
260:S2CID
134:carry
717:Gout
629:of
569:1675
529:MeSH
518:OMIM
481:PMID
432:PMID
414:ISSN
373:PMID
338:PMID
330:ISSN
295:PMID
287:ISSN
252:PMID
217:PMID
101:and
587:NIH
585:at
471:PMC
463:doi
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207:PMC
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