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CASE REPORT article
Front. Pharmacol.
Sec. Pharmacogenetics and Pharmacogenomics
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1459565
Case Report: A case of severe capecitabine toxicity due to confirmed in trans compound heterozygosity of a common and rare DPYD variant
Provisionally accepted- 1 Department of Medical Oncology, University Hospital Brussels, Brussels, Belgium
- 2 Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Brussels, Belgium
- 3 Pharmacy department, University Hospital Brussels, Brussels, Belgium
- 4 Centre for Medical Genetics, Vrije Universiteit Brussel (VUB) - Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium., Brussels, Belgium
- 5 Louvain centre for Toxicology and Applied Pharmacology, Institute for Experimental and Clinical Research,Université catholique de Louvain, Brussles, Belgium
- 6 Department of Medical Biochemistry, University Hospital Saint-Luc, Woluwe-Saint-Lambert, Brussels, Belgium
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.
Keywords: case report, capecitabine, DPYD gene polymorphism, Pheno-and genotyping, rare variant
Received: 04 Jul 2024; Accepted: 09 Sep 2024.
Copyright: © 2024 De Haar-Holleman, Cortoos, Vlaeminck, Van Landuyt, Steurbaut, Vaeyens and Haufroid. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Pieter-Jan Cortoos, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, 1050, Brussels, Belgium
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