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DPD deficiency

Having a DPD deficiency could make the side effects of certain chemotherapy drugs worse. This group of drugs are called fluoropyrimidines. Examples include fluorouracil and capecitabine.

What is DPD deficiency?

DPD stands for dihydropyrimidine dehydrogenase. It is an enzyme made by the liver that helps our body break down thymine and uracil. Thymine and uracil make up part of the structure of our genes.

DPD deficiency happens when we have low or no levels of the DPD enzyme.  It is very rare to have no DPD (a complete DPD deficiency) but it is slightly more common to have low or very low levels (a partial deficiency). 

Between 3 and 5 out of every 100 people (3 to 5%) have a partial DPD deficiency.

A partial DPD deficiency doesn’t usually cause symptoms and so you won’t know if you have it. People with a severe or complete DPD deficiency usually start to have symptoms as babies. They might have:

  • fits (seizures)
  • a small head size (microcephaly)
  • problems with their development such as walking and talking

DPD deficiency and the side effects of capecitabine and fluorouracil

The DPD enzyme helps our body to break down fluorouracil (also known as 5FU) and capecitabine (also known as Xeloda). Fluorouracil and capecitabine are two common chemotherapy drugs. They are used as a treatment for a number of different cancers, including breast, bowel and stomach cancer.

Without enough of the DPD enzyme, these chemotherapy drugs build up in our body and cause more severe side effects than usual.  In some situations, these side effects could be life threatening. The side effects include:

  • a drop in the level of blood cells increasing your risk of having infections, breathlessness and bleeding
  • diarrhoea
  • a sore mouth
  • feeling or being sick
  • a severe skin reaction which leads to peeling or blistering of the skin

Between 10 and 20 out of every 100 people (10 and 20%) have severe side effects from fluorouracil and capecitabine. But not everyone has a DPD deficiency. So, it is important to speak to your doctor about all the side effects you have. 

So far, research has shown that people with DPD deficiency usually develop severe side effects after the first few doses of fluorouracil or capecitabine.

Testing for DPD deficiency

At the moment, people having fluorouracil or capecitabine do not have routine testing for DPD before their treatment.

There are tests available, but they are not completely reliable. For instance, they do not find everyone who is likely to have serious side effects. For a test to become standard it needs to be:

  • accurate
  • quick
  • easy to do
  • cost effective

You might have the test through the NHS if your doctor thinks you need it. For example, if you are having treatment with fluorouracil or capecitabine and you have severe side effects. Some clinics offer this test privately. But we are not able to recommend any one clinic.

Talk to your doctor if you are worried about DPD deficiency and if you think you should have this test.

Researchers are trying to find a test that is better at predicting who will have serious side effects. And NHS England are looking at the available research to decide whether routine testing should take place.

Research into DPD deficiency testing

Doctors are looking at a number of different ways to test for DPD deficiency. 

Research looking into the DPYD gene

The DPYD gene helps to control the production of DPD in our bodies. Doctors know that there are a number of changes (mutations) in the DPYD gene that can cause DPD deficiency.

But not everyone who has severe side effects to fluorouracil and capecitabine has changes in the DPYD gene. There might be other changes that can also have an effect on how we break down these chemotherapy drugs.    

Research looking into the levels of uracil and dihydrouracil

Doctors know that people with DPD deficiency have high levels of uracil and low levels of a substance called dihydrouracil. So they have developed tests that measure the levels of these two substances in your blood and urine.

More research needs to be done to find out how effective these tests are.

Research looking into breath tests

Doctors can diagnose a number of conditions by measuring the amount of certain gases that we breathe out. This test involves drinking a substance that is usually broken down by different enzymes, including DPD. As this substance is broken down by the enzymes, a gas called CO2 is produced. Doctors can then measure the amount of CO2 we breathe out.

Breath tests are still at very early stages of development and they are currently very expensive.

Last reviewed: 
29 Nov 2018
  • Should DPD analysis be required prior to prescribing fluoropyrimidines?
    Jane Yen and Howard McLeod
    European Journal of Cancer, 2007. Vol 42, Pages 1011-1016

  • Prevention of 5-fluorouracil-induced early severe toxicity by pre-therapeutic dihydropyrimidine dehydrogenase deficiency screening: assessment of a multiparametric approach
    Boisdron-Celle and others
    Seminars in Oncology, 2017. Vol 44, Issue 1

  • Clinical Pharmacogenetics Implementation Consortium Guidelines for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing
    K. Caudle and others
    Clinical Pharmacology and Therapeutics, 2013. Vol 94, Issue 6, Pages 640-645

  • Your Guide to Understanding Genetic Conditions - Dihydropyrimidine dehydrogenase deficiency
    NHI US National Library of Medicine, Accessed October 2018

  • Routine Dehydropyrimidine Dehydrogenase Testing for Anticipating 5-Fluorouracil-Related Severe Toxicities: Hype or Hope?
    J Ciccoline and others
    Clinical Colorectal Cancer, 2010. Vol 9, Issue 4, Pages 224-228

  • Capecitabine: risk of severe skin reactions – discontinue treatment
    Medicines and Healthcare Products Regulatory Agency (MHRA), January 2014

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