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), capecitabine and tegafur.

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, 5FU and tegafur

The DPD enzyme helps our body to break down 5FU, capecitabine (also known as Xeloda) and tegafur (also known as tegafur-uracil and UFT). 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)
  • bile duct
  • pancreas
  • neuroendocrine tumours or neoplasms

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

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 within the first 2 treatment cycles. 

Is there a test to check for DPD deficiency?

Yes there is a test. All people having 5FU, capecitabine or tegafur should have a blood test before their treatment to check if they have a DPD deficiency.

Research into DPD deficiency testing

Doctors and scientists are looking at learning more about the DPYD gene and at a number of different 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.

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