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Genetic and Rare Diseases Information Center (GARD)

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Dihydropyrimidine dehydrogenase deficiency


Other Names for this Disease

  • DPD deficiency
  • Familial pyrimidinemia
  • Hereditary thymine-uraciluria
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Your Question

I recently found out I was a carrier. I would like to be clear that I can only pass the disease on to a child if the father is also a carrier. Lastly I am still a little confused when it comes to how it affects exposure to 5-fluorouracil. Does this mean that if I were to get cancer in the future I would not be able to be treated with chemotherapy?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

How is dihydropyrimidine dehydrogenase deficiency inherited?

Dihydropyrimidine dehydrogenase (DPD) deficiency is inherited in an autosomal recessive manner. This means that in affected individuals, both copies of the DPYD gene in each cell (one inherited from each parent) have mutations. The mutations that cause DPD deficiency vary widely in severity; therefore, some people with 2 mutated copies of the gene may have signs and symptoms of the condition, while others may be asymptomatic. However, all individuals with 2 mutations are at risk for toxic reactions to fluoropyrimidine drugs.[1]

Individuals who carry one mutated copy of the disease-causing gene (including most parents of affected individuals) are referred to as carriers. Carriers typically do not have signs and symptoms of the condition. However, people with one mutated copy of the DPYD gene may still experience toxic reactions to fluoropyrimidine drugs.[1]

When 2 carriers for the same autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each parent, and a 25% risk to not have the condition and not be a carrier. A child of one carrier parent has a 50% risk to also be a carrier.
Last updated: 8/20/2012

Can people with mutations in the gene that causes dihydropyrimidine dehydrogenase deficiency have chemotherapy?

People with dihydropyrimidine dehydrogenase (DPD) deficiency, including people who do not have signs and symptoms, are at risk for severe, toxic reactions to specific drugs called fluoropyrimidines, which are used in some chemotherapy regimes to treat cancer. Examples include 5-fluorouracil (5-FU) and capecitabine. People with DPD deficiency cannot effectively break down and eliminate these drugs from the body, so they can build up to toxic levels.[1]

Individuals with a partial DPD deficiency (about 3% to 5% of the population) due to sequence variations in DPYD gene, as well as people with one mutated copy of the DPYD gene (carriers), also may have limited ability to fully metabolize the drug.[2][1] It has been suggested that individuals with known DPD deficiency and/or a family history of known mutations in the DPYD gene avoid therapy with these drugs. These individuals may consider treatment regimens that do not contain 5-FU or other fluoropyrimidines (if available). In some cases, modified doses of these drugs may still be recommended.[2]

Fluoropyrimidines are only one of various types of chemotherapy drugs that may be used to treat an individual with cancer. Several factors influence which drugs may be used and may include the type of cancer; the stage of the cancer (how far it has spread); the patient’s age; the patient’s general state of health; other serious health problems; and/or types of cancer treatments given in the past.[3]

Information about different types of chemotherapy drugs is available on the American Cancer Society's Web site and can be viewed by clicking here.
Last updated: 8/22/2012

References
Other Names for this Disease
  • DPD deficiency
  • Familial pyrimidinemia
  • Hereditary thymine-uraciluria
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.