Dihydropyrimidine Dehydrogenase Deficiency

An autosomal recessive disorder affecting DIHYDROPYRIMIDINE DEHYDROGENASE and causing familial pyrimidinemia. It is characterized by thymine-uraciluria in homozygous deficient patients. Even a partial deficiency in the enzyme leaves individuals at risk for developing severe 5-FLUOROURACIL-associated toxicity.

Also Known As:

DPD Deficiency; Dihydropyrimidinuria; Familial Pyrimidemia; Familial Pyrimidinemia; Hereditary Thymine-Uraciluria; Pyrimidinemia, Familial; Thymine-Uraciluria, Hereditary; DPD Deficiencies; Deficiencies, DPD; Deficiencies, Dihydropyrimidine Dehydrogenase; Deficiency, DPD; Deficiency, Dihydropyrimidine Dehydrogenase; Dehydrogenase Deficiencies, Dihydropyrimidine; Dehydrogenase Deficiency, Dihydropyrimidine; Dihydropyrimidine Dehydrogenase Deficiencies; Dihydropyrimidinurias; Familial Pyrimidemias; Familial Pyrimidinemias; Hereditary Thymine Uraciluria; Hereditary Thymine-Uracilurias; Pyrimidemia, Familial; Pyrimidemias, Familial; Pyrimidinemias, Familial; Thymine Uraciluria, Hereditary; Thymine-Uracilurias, Hereditary

Networked: 283 relevant articles (4 outcomes, 21 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Genetic Predisposition to Disease (Genetic Predisposition)
2.	Neoplasms (Cancer)
3.	Colorectal Neoplasms (Colorectal Cancer)
4.	Colonic Neoplasms (Colon Cancer)
5.	Breast Neoplasms (Breast Cancer)

Experts

1.	van Kuilenburg, André B P: 19 articles (01/2022 - 05/2002)
2.	Ciccolini, Joseph: 16 articles (01/2020 - 08/2006)
3.	Diasio, Robert B: 12 articles (06/2022 - 03/2002)
4.	Lacarelle, Bruno: 10 articles (01/2020 - 08/2006)
5.	Meijer, Judith: 10 articles (01/2019 - 01/2008)
6.	van Gennip, A H: 10 articles (01/2006 - 01/2000)
7.	Meinsma, Rutger: 9 articles (01/2019 - 05/2002)
8.	Zoetekouw, Lida: 8 articles (01/2018 - 09/2002)
9.	van Kuilenburg, A B P: 8 articles (01/2017 - 01/2003)
10.	van Kuilenburg, A B: 8 articles (03/2004 - 01/2000)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Dihydropyrimidine Dehydrogenase Deficiency:

1.	Fluorouracil (Carac)FDA LinkGeneric 01/01/2021 - "Dihydropyrimidine dehydrogenase deficiency in patients with severe toxicity after 5-fluorouracil: a retrospective single-center study." 03/01/2012 - "The aim of this study was to evaluate the pharmacokinetics of 5FU and to develop a limited sampling strategy to detect decreased 5FU elimination in patients with a c.1905+1G>A-related DPD deficiency. " 08/01/2004 - "Extensive studies have associated both profound and partial deficiency in DPD activity with severe, unanticipated toxicity after 5-FU administration, while research on the molecular basis behind DPD deficiency has been linked to various sequence variants of the DPYD gene. " 07/24/1998 - "Population and family studies of dihydropyrimidinuria: prevalence, inheritance mode, and risk of fluorouracil toxicity." 01/01/2023 - "The case report highlights the importance of TDM in administering 5-FU to patients with partial DPD deficiency, as it allows individualized dosing and prevents severe toxicity."
2.	Dihydrouracil Dehydrogenase (NADP) (Dihydropyrimidine Dehydrogenase)IBA 02/06/2022 - "The dihydropyrimidine dehydrogenase (DPYD) gene encodes DPD, and studies suggest that DPYD polymorphisms can result in DPD deficiency. " 01/01/2022 - "To characterize biobank participants' understanding of PGx research results, we conducted a focus group study, which took place after PGx variants conferring increased risk of dihydropyrimidine dehydrogenase (DPD) deficiency were disclosed to biobank contributors. " 01/01/2023 - "In 2020, the European Medicines Agency recommended testing patients for dihydropyrimidine dehydrogenase (DPD) deficiency before systemic treatment with fluoropyrimidines (FP). " 01/01/2023 - "Dihydropyrimidine dehydrogenase (DPD) deficiency screening is a pre-therapeutic standard to prevent severe fluoropyrimidine-related toxicity. " 10/06/2022 - "Dihydropyrimidine dehydrogenase (DPD) deficiency is associated with severe fluoropyrimidines-induced toxicity. "
3.	uridine triacetateIBA 01/01/2018 - "We found that uridine triacetate was effective both in the 5-FU overdose and DPD deficiency models. " 04/01/2018 - "This review summarizes the current state of knowledge of FIC with special regard to proposed pathogenetic models (coronary vasospasm, endothelium and cardiomyocytes damage, toxic metabolites, dihydropyrimidine dehydrogenase deficiency); risk and predictive factors; efficacy and usefulness in detection of laboratory markers, electrocardiographic changes and cardiac imaging; and specific treatment, including a novel agent, uridine triacetate. " 01/01/2018 - "In this study we used mouse models of 5-FU overdose and of dihydropyrimidine dehydrogenase (DPD) deficiency to compare the efficacy of uridine triacetate in reducing toxicity and mortality when treatment was initiated at time points from 4 to 144 h after administration of 5-FU. " 01/01/2018 - "Prompt treatment with uridine triacetate improves survival and reduces toxicity due to fluorouracil and capecitabine overdose or dihydropyrimidine dehydrogenase deficiency." 01/01/2019 - "We report and discuss the management and outcome of capecitabine toxicity with the recently FDA approved antidote, uridine triacetate (Vistogard), in a 57-year-old female breast cancer patient with homozygous dihydropyrimidine dehydrogenase deficiency who received treatment beyond the recommended 96 h window from the last dose of capecitabine."
4.	Oxidoreductases (Dehydrogenase)IBA 06/01/2010 - "Because of the loss of efficacy of this treatment following initial success, coupled with its poorly evaluated safety, caution must be exercised when prescribing it, particularly in patients with dihydropyriminidine dehydrogenase (DPD) deficiency or for use on damaged skin." 03/01/2004 - "Genotyping revealed that she carried the exon 14-skipping mutation which is known to result in dehydropyrimidine dehydrogenase (DPD) deficiency. " 09/25/2023 - "The increased risk of severe and life-threatening toxicity in patients with dihydropyridine dehydrogenase (DPD) deficiency, under treatment with fluoropyrimidines, has been widely studied. " 01/01/2019 - "Dihydropryimidine dehydrogenase (DPD) deficiency is a pharmacogenetic syndrome associated with severe or lethal toxicities with oral capecitabine. " 01/01/2022 - "While standard doses of 5-fluorouracil and capecitabine are safe for most patients, the risk of severe toxicity is increased for the approximately 6% of patients with dihydropyimidine dehydrogenase (DPD) deficiency caused by pathogenic DPYD gene variants. "
5.	CarbonIBA 05/01/2002 - "Porous graphitic carbon shows promise for the rapid screening partial DPD deficiency in lymphocyte dihydropyrimidine dehydrogenase in Chinese, Indian and Malay in Singapore by using semi-automated HPLC-radioassay."
6.	eniluracilIBA 01/01/1997 - "Based on allometric analysis, the estimated clearance of 5-FU (10.9 l/h) in humans with DPD deficiency was comparable to the observed values in humans lacking DPD activity due to genetic predisposition (10.1 l/h), or treatment with 776C85 (7.0 l/h) or (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdUrd, 6.6 l/h). "
7.	brivudine (brivudin)IBA 01/01/1997 - "Based on allometric analysis, the estimated clearance of 5-FU (10.9 l/h) in humans with DPD deficiency was comparable to the observed values in humans lacking DPD activity due to genetic predisposition (10.1 l/h), or treatment with 776C85 (7.0 l/h) or (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdUrd, 6.6 l/h). "
8.	UracilIBA 06/21/2022 - "It also studies the incidence of adverse events (AEs) in patients with DPD deficiency established with plasmatic uracil determination. " 06/21/2022 - "This study seeks to analyse the correlation between DPD deficiency and plasmatic uracil values in patients who are candidates for a fluoropyrimidine scheme. " 01/01/2016 - "Loading studies with uracil to identify patients with a DPD deficiency warrants further investigation." 11/01/2007 - "Data presented in this study demonstrate that alterations of uracil catabolism are not limited to DPD deficiency, and that inactivating mutations in DHP might impair uracil catabolism in cases of normal DPD activity." 01/01/2023 - "In 2020, the European Medicines Agency (EMA) recommended two methods for pre-treatment DPD deficiency testing in clinical practice: phenotyping using endogenous uracil concentration or genotyping for DPYD risk variant alleles. "
9.	EnzymesIBA 09/01/2004 - "The variability of DPD enzyme activity in population studies and the different DPYD alleles together with new phenotypic and genotypic methods of screening for DPD deficiency will also be reviewed." 08/01/2003 - "Several studies examining the molecular basis for DPD deficiency have identified over 30 sequence variations in the DPYD gene (which codes for the DPD enzyme). " 01/01/2022 - "DPD deficiency testing later resulted as heterozygous for IVS14+1G>A allele indicating enzyme deficiency. " 01/01/2020 - "Whole exon sequencing of DPYD in patients with suspicion of partial DPD deficiency can help to identify rare or new variants that lead to enzyme inactivation. " 01/01/2019 - "This analysis identified the variants c.85T>C and c.496A>G, which were previously described as pivotal components of the haplotype associated with decreased enzyme activity and suggested that both variant alleles are related to DPD deficiency. "
10.	dihydrouracilIBA 01/01/2023 - "In this study, we aimed to refine the pre-analytical recommendations for determining U and dihydrouracil (UH2 ) concentrations, as they are essential in reliable DPD-deficiency testing. " 06/01/2012 - "Assays showing that DPD deficiency impairs breakdown of Ura to dihydrouracil (UH(2)) seem promising for clinical use. " 04/01/2022 - "The available methods in routine to screen for DPD deficiency were analyzed and discussed in several group meetings involving members of the oncological, genetic and toxicological societies in Belgium: targeted genotyping based on the detection of 4 DPYD variants and phenotyping, through the measurement of uracil and dihydrouracil/uracil ratio in plasma samples. " 05/01/2018 - "DPD levels were analysed through determining the ratio of plasma uracil (U) and dihydrouracil (UH2) by HPLC, and the results indicated a mild DPD deficiency in the patients with HCC. " 02/01/2016 - "The patient's dihydrouracil/uracil ratio indicates complete DPD deficiency. "

Therapies and Procedures

1.	Drug Therapy (Chemotherapy) 06/30/2022 - "An appreciable fraction of patients with DPD deficiency that receive 5-FU-based chemotherapy die as a result of toxicity. " 08/13/2021 - "Dihydropyrimidine dehydrogenase deficiency is a major cause of severe fluoropyrimidine-induced toxicity and could lead to interruption of chemotherapy or life-threatening adverse reactions. " 03/22/2019 - "Dihydropyrimidine dehydrogenase deficiency secondary to polymorphisms in the DPYD gene can lead to significant toxicity associated with the administration of fluoropyrimidine chemotherapy. " 04/01/2018 - "Currently, there is no regulatory obligation for DPD deficiency screening in patients scheduled to receive a fluoropyrimidine-based chemotherapy. " 04/01/2018 - "[Dihydropyrimidine déhydrogenase (DPD) deficiency screening and securing of fluoropyrimidine-based chemotherapies: Update and recommendations of the French GPCO-Unicancer and RNPGx networks]."
2.	Therapeutics 05/01/2019 - "To date, pre-treatment screening for DPD deficiency in patients with planned 5-fluorouracil-based therapy is not a standard of care. " 05/08/2007 - "These data support the future use of this approach, suitable to clinical practice, as screening test to identify DPD deficiency before 5-FU-based therapy." 01/15/2006 - "These pharmacokinetic data further support the future use of the UraBT as a screening test to identify DPD deficiency before 5-fluorouracil-based therapy." 10/25/2001 - "A new HPLC method with direct UV detection for the determination of 5FUH2 in peripheral lymphocytes has been developed to detect DPD deficiency in patients treated with 5FU-based therapy. " 03/01/2006 - "Taking into account the relatively small impact of adjuvant 5FU-based chemotherapy on survival, patients should be informed about the risks of the therapy and should be offered the possibility of testing for the presence of a DPD deficiency in advance of receiving such treatment."
3.	Adjuvant Chemotherapy 11/01/2018 - "[A Case of Colon Cancer with DPD Deficiency That Showed Severe Myelosuppression by CapeOX Adjuvant Chemotherapy after Colon Resection]." 01/01/2010 - "[Severe bone marrow suppression during adjuvant chemotherapy for gastric cancer by S-1 and its possible relationship to dihydropyrimidine dehydrogenase deficiency]." 01/01/2022 - "Among patients receiving adjuvant chemotherapy for stage 3 colon cancer, screening for DPD deficiency with DPYD genotyping is a cost-effective strategy for preventing infrequent but severe and sometimes fatal toxicities of fluoropyrimidine chemotherapy." 01/01/2015 - "[Suspected dihydropyrimidine dehydrogenase deficiency in a patient receiving capecitabine as adjuvant chemotherapy after colon resection]." 12/01/2021 - "[A Case of Colon Cancer with Suspected DPD Deficiency Causing Severe Adverse Effects following Adjuvant Chemotherapy with Capecitabine]."
4.	Drug Tapering 09/01/2018 - "It is now well established that DPD deficiency could lead to severe toxicities and, thus, require dose reduction in deficient patients. " 01/01/2018 - "Upfront screening for DPD deficiency and dose reduction in patients with partial DPD deficiency is recommended and improves patient safety. " 10/01/2016 - "Patients homozygous for DPYD c.1129-5923C>G/haplotype B3 have partial DPD deficiency and require a dose reduction when treated with fluoropyrimidines." 06/21/2022 - "Patients who had a DPD deficiency according to plasmatic uracil measurements were started on a 5-fluorouracil (5-FU) regimen with a dose reduction of 15-50% (mean 35%). "
5.	Aftercare (After-Treatment) 10/01/2018 - "Here we present a case of a patient who had a fatal outcome after treatment with 5-FU who was found to have an unknown DPD deficiency discovered at autopsy." 08/01/1999 - "We now report the first known cancer patient who developed life-threatening complications after treatment with topical 5-FU and was shown subsequently to have profound DPD deficiency. " 03/27/2004 - "[Severe toxicity after treatment with capecitabine and fluorouracil due to partial dihydropyrimidine dehydrogenase deficiency]."