Case report: A case of severe capecitabine toxicity due to confirmed in trans compound heterozygosity of a common and rare DPYD variant
Variations in the activity of the enzyme dihydropyrimidine dehydrogenase (DPD) are associated with toxicity to fluoropyrimidine-containing chemotherapy. Testing of DPD deficiency either by targeted genotyping of the corresponding DPYD gene or by quantification of plasma concentration of uracil and d...
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Frontiers Media S.A.
2024-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1459565/full |
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| author | Amy de Haar-Holleman Amy de Haar-Holleman Pieter-Jan Cortoos Pieter-Jan Cortoos Jelle Vlaeminck Paulien Van Landuyt Stephane Steurbaut Stephane Steurbaut Freya Vaeyens Vincent Haufroid Vincent Haufroid |
| author_facet | Amy de Haar-Holleman Amy de Haar-Holleman Pieter-Jan Cortoos Pieter-Jan Cortoos Jelle Vlaeminck Paulien Van Landuyt Stephane Steurbaut Stephane Steurbaut Freya Vaeyens Vincent Haufroid Vincent Haufroid |
| author_sort | Amy de Haar-Holleman |
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| description | Variations in the activity of the enzyme dihydropyrimidine dehydrogenase (DPD) are associated with toxicity to fluoropyrimidine-containing chemotherapy. Testing of DPD deficiency either by targeted genotyping of the corresponding DPYD gene or by quantification of plasma concentration of uracil and dihydrouracil (phenotyping approach) are the two main methods capable of predicting reduced enzymatic activity in order to reduce adverse reactions after fluoropyrimidine treatment. In this paper, we describe a patient with locally advanced colon carcinoma with severe toxicity following capecitabine therapy. Whereas targeted genotyping for the 4 most common DPYD variants analysis revealed heterozygous presence of the c.2846A>T variant, which is a relatively common variant associated with a partial deficiency, additional phenotyping was compatible with a complete DPD deficiency. Subsequent sequencing of the whole DPYD gene revealed the additional presence of the rare c.2872A>G variant, which is associated with a total loss of DPD activity. A clinical case of in trans compound heterozygosity of a common and a rare DPYD variant (c.2846A>T and c.2872A>G) has, to the best of our knowledge, not been previously described. Our case report shows the importance of performing either preemptive phenotyping or preemptive complete genetic analysis of the DPYD gene for patients planned for systemic fluoropyrimidines to identify rare and low frequency variants responsible for potentially life-threatening toxic reactions. |
| format | Article |
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| issn | 1663-9812 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-7e18b3da531047aab7807db6f624bd1d2025-08-20T02:17:25ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-09-011510.3389/fphar.2024.14595651459565Case report: A case of severe capecitabine toxicity due to confirmed in trans compound heterozygosity of a common and rare DPYD variantAmy de Haar-Holleman0Amy de Haar-Holleman1Pieter-Jan Cortoos2Pieter-Jan Cortoos3Jelle Vlaeminck4Paulien Van Landuyt5Stephane Steurbaut6Stephane Steurbaut7Freya Vaeyens8Vincent Haufroid9Vincent Haufroid10Department of Medical Oncology, Universitair Ziekenhuis Brussel (UZBrussel), Brussels, BelgiumTranslational Oncology Research Center (TORC), Vrije Universiteit Brussel (VUB), Brussels, BelgiumPharmacy Department, Universitair Ziekenhuis Brussel (UZBrussel), Brussels, BelgiumFaculty of Medicine & Pharmacy, Vrije Universiteit Brussel (VUB), Brussels, BelgiumCentre for Medical Genetics, Research Group Genetics, Reproduction and Development, Clinical Sciences, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, BelgiumPharmacy Department, Universitair Ziekenhuis Brussel (UZBrussel), Brussels, BelgiumPharmacy Department, Universitair Ziekenhuis Brussel (UZBrussel), Brussels, BelgiumFaculty of Medicine & Pharmacy, Vrije Universiteit Brussel (VUB), Brussels, BelgiumCentre for Medical Genetics, Research Group Genetics, Reproduction and Development, Clinical Sciences, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, BelgiumLouvain Center for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, BelgiumDepartment of Clinical Chemistry, Cliniques Universitaires Saint-Luc, Brussels, BelgiumVariations in the activity of the enzyme dihydropyrimidine dehydrogenase (DPD) are associated with toxicity to fluoropyrimidine-containing chemotherapy. Testing of DPD deficiency either by targeted genotyping of the corresponding DPYD gene or by quantification of plasma concentration of uracil and dihydrouracil (phenotyping approach) are the two main methods capable of predicting reduced enzymatic activity in order to reduce adverse reactions after fluoropyrimidine treatment. In this paper, we describe a patient with locally advanced colon carcinoma with severe toxicity following capecitabine therapy. Whereas targeted genotyping for the 4 most common DPYD variants analysis revealed heterozygous presence of the c.2846A>T variant, which is a relatively common variant associated with a partial deficiency, additional phenotyping was compatible with a complete DPD deficiency. Subsequent sequencing of the whole DPYD gene revealed the additional presence of the rare c.2872A>G variant, which is associated with a total loss of DPD activity. A clinical case of in trans compound heterozygosity of a common and a rare DPYD variant (c.2846A>T and c.2872A>G) has, to the best of our knowledge, not been previously described. Our case report shows the importance of performing either preemptive phenotyping or preemptive complete genetic analysis of the DPYD gene for patients planned for systemic fluoropyrimidines to identify rare and low frequency variants responsible for potentially life-threatening toxic reactions.https://www.frontiersin.org/articles/10.3389/fphar.2024.1459565/fullcase reportcapecitabineDPYD gene polymorphismpheno- and genotypingrare variant |
| spellingShingle | Amy de Haar-Holleman Amy de Haar-Holleman Pieter-Jan Cortoos Pieter-Jan Cortoos Jelle Vlaeminck Paulien Van Landuyt Stephane Steurbaut Stephane Steurbaut Freya Vaeyens Vincent Haufroid Vincent Haufroid Case report: A case of severe capecitabine toxicity due to confirmed in trans compound heterozygosity of a common and rare DPYD variant Frontiers in Pharmacology case report capecitabine DPYD gene polymorphism pheno- and genotyping rare variant |
| title | Case report: A case of severe capecitabine toxicity due to confirmed in trans compound heterozygosity of a common and rare DPYD variant |
| title_full | Case report: A case of severe capecitabine toxicity due to confirmed in trans compound heterozygosity of a common and rare DPYD variant |
| title_fullStr | Case report: A case of severe capecitabine toxicity due to confirmed in trans compound heterozygosity of a common and rare DPYD variant |
| title_full_unstemmed | Case report: A case of severe capecitabine toxicity due to confirmed in trans compound heterozygosity of a common and rare DPYD variant |
| title_short | Case report: A case of severe capecitabine toxicity due to confirmed in trans compound heterozygosity of a common and rare DPYD variant |
| title_sort | case report a case of severe capecitabine toxicity due to confirmed in trans compound heterozygosity of a common and rare dpyd variant |
| topic | case report capecitabine DPYD gene polymorphism pheno- and genotyping rare variant |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1459565/full |
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