DPD deficiency

What is DPD deficiency?

DPD stands for dihydropyrimidine dehydrogenase. It is an ​enzyme​ the liver makes that helps the body break down thymine and uracil. Thymine and uracil make up part of the structure of our ​genes​ . 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 you don’t usually know that you have the deficiency unless you have 5FU or capecitabine.

People with 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 fluorouracil (5FU) and capecitabine (also known as Xeloda). Fluorouracil (5FU) and capecitabine are two common chemotherapy drugs. They are used as a treatment for several different cancers, including:

• breast

• bowel

• head and neck

• stomach

• back passage (anus)

• bile duct

• pancreas

• neuroendocrine tumours or neoplasms

Without enough DPD enzyme, these chemotherapy drugs build up in the 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

• soreness, redness and peeling on palms and soles of feet

Between 20 and 30 out of every 100 people (20 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 your side effects. 

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?

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