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 fluorouracil (5FU) and capecitabine (also known as Xeloda).

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 also known as a complete DPD deficiency. It is more common to have low or very low levels also known as a partial deficiency. Between 2 and 8 out of every 100 people (between 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:

• seizures (fits)

• a small head size (microcephaly)

• problems with their development, such as walking and talking

• too much muscle tone (hypertonia), this makes their arms and legs stiff and difficult to move

DPD deficiency and the side effects of capecitabine and 5FU

The DPD enzyme helps our body to break down 5FU and capecitabine. 5FU and capecitabine are treatments 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, this increases your risk of getting infections, breathlessness and bleeding

• diarrhoea which can be severe

• inflammation of the digestive system – symptoms can include mouth sores and ulcers, tummy (abdominal) pain, feeling or being sick, bleeding gums or passing blood when you poo

• feeling or being sick which can lead to dehydration

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

• hair loss

In England between 10 and 40 out of every 100 people (between 10 and 40%) have severe side effects from 5FU and capecitabine. In about 1 in every 100 people (about 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 during the first cycle. Or after the dose of the drugs have gone up.

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.

Research into treatment for people with DPD deficiency testing

Researchers abroad are looking to see if it is safe to replace fluoropyrimidines with another chemotherapy called trifluridine and tipiracil (Lonsurf) for people with a DPD deficiency. This is for people who have advanced cancer of the:

• bowel

• stomach

• food pipe (oesophagus)

• gastro oesophageal junction

Other researchers want to work out if they can tailor the amount on fluoropyrimidine a person receives based of their uracilemia measurement. This is the level of uracil in the blood. Doctors use it to work out if you have a DPD deficiency or not.