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DPD deficiency

Having a deficiency in the DPD enzyme could make the side effects of certain chemotherapy drugs worse. For some people, these side effects can be life threatening. This group of drugs are called fluoropyrimidines. Examples include 5-fluorouracil (5FU) 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. Genes are coded messages that tell cells how to behave. Uracil is also an important part of the drugs 5FU and capecitabine.

DPD deficiency happens when we have low or no levels of the DPD enzyme. The cause of this is usually changes (mutations) in the DPYD gene.

It is very rare to have no DPD in the body (a complete DPD deficiency) but it is more common to have low or very low levels (a partial deficiency). Between 2 and 8 out of every 100 people (2 to 8%) have a partial DPD deficiency.

A partial DPD deficiency doesn’t usually cause symptoms. This means that you don’t usually know that you have the deficiency unless you have 5FU or capecitabine.

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 5FU

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

  • breast
  • bowel
  • head and neck
  • stomach
  • back passage (anus)

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 can be life threatening. The side effects include:

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

Between 10 and 30 out of every 100 people (10 and 30%) have severe side effects from 5FU and capecitabine. Less than 1 in every 100 people (less than 1%) who have 5FU and capecitabine die from their treatment. But not everyone has a DPD deficiency. So, it is important to speak with your doctor about all the side effects you have. 

So far, research has shown that people with DPD deficiency usually develop severe side effects to 5FU or capecitabine after the first 2 treatment cycles. 

What tests can I have for DPD deficiency?

At the moment, most people having 5FU or capecitabine do not have routine testing for DPD before their treatment.

There are some tests available, but how effective they are can vary. For instance, some tests do not find everyone who is likely to have serious side effects. The test is a blood test that you can have at the same time as other blood tests you are having.

Some but not all NHS hospitals have now started to test everyone who is going to have 5FU or capecitabine. This is because the NHS is still looking at the available research to decide whether routine testing should take place. 

Some clinics and private health care insurers 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.

Research into DPD deficiency testing

Doctors and scientist are looking at learning more about the DPYD gene and at a number of tests for DPD deficiency. 

Research looking into the DPYD gene

The DPYD gene helps to control the production of DPD in our bodies. Doctors already know a lot about the DPYD gene. They know there are a number of changes (mutations) in this 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 usually have high levels of uracil and low levels of a substance called dihydrouracil in their bodies. So scientists 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 the DPD enzyme. As this substance is broken down by the enzyme, a gas called CO2 is produced. Doctors can then measure the amount of CO2 we breathe out to try to find the level of DPD in the body.

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

Last reviewed: 
13 Aug 2019
  • 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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