Dehydropyrimidine dehydrogenase deficiency in a cancer patient undergoing 5-fluorouracil chemotherapy

We present a case of a Caucasian cancer patient undergoing 5-fluorouracil (5-FU)-containing chemotherapy in our department. The 49-year-old female patient suffered from adverse effects representing WHO grade 3 toxicity. Genotyping revealed that she carried the exon 14-skipping mutation which is known to result in dehydropyrimidine dehydrogenase (DPD) deficiency. DPD is the enzyme that converts 5-FU to inactive metabolites and therefore dictates the amount of 5-FU that is available to be metabolised to cytotoxic nucleotides. Consequently DPD deficiency is the cause of severe adverse and sometimes lethal reactions to 5-FU. In conclusion the identification of cancer patients at increased risk of severe toxicity prior to the administration of 5-FU would be desirable.