Overview
DPD Gene Mutation, also known as Dihydropyrimidine Dehydrogenase (DPD) deficiency, is a genetic condition that affects the body’s ability to break down certain chemotherapy drugs, especially fluoropyrimidines such as 5-Fluorouracil (5-FU) and related medicines. The DPD enzyme plays a critical role in metabolizing pyrimidines, which are essential components of DNA and RNA. When this enzyme does not function properly due to a gene mutation, toxic levels of these drugs can accumulate in the body.
The DPD gene, scientifically identified as DPYD, is located on chromosome 1. Mutations in this gene can lead to partial or complete enzyme deficiency. Individuals with this condition may remain unaware of the mutation until they are exposed to fluoropyrimidine-based chemotherapy, where the deficiency becomes clinically significant. Because of its strong impact
on treatment safety, DPD gene mutation testing is often referred to as a 5-FU toxicity test and is used to guide safer chemotherapy planning.Symptoms
Symptoms of DPD gene mutation vary widely depending on whether the enzyme deficiency is partial or complete. Some individuals may remain asymptomatic throughout life, while others develop severe reactions when exposed to fluoropyrimidine drugs.
Common symptoms include severe toxicity following chemotherapy, such as intense gastrointestinal reactions, mucositis, and bone marrow suppression. Neurological symptoms may also occur, including seizures, developmental delay, movement disorders, and muscle weakness. In some cases, affected individuals experience impaired motor development, poor muscle tone, or coordination problems.
Eye abnormalities and intellectual disability have also been reported in more severe forms. After exposure to fluoropyrimidines, patients may develop hand-foot syndrome, low blood cell counts, and extreme fatigue. The severity and timing of symptoms depend on enzyme activity levels and drug exposure.
Causes
The primary cause of DPD gene mutation is a change in the DPYD gene, which leads to reduced or absent activity of the DPD enzyme. This enzyme is responsible for breaking down uracil, thymine, and fluoropyrimidine drugs into inactive substances that can be safely eliminated from the body.
More than one type of mutation can affect this gene, and each mutation impacts enzyme activity differently. Some mutations result in complete enzyme loss, while others cause partial reduction in function. Because the condition follows an autosomal recessive inheritance pattern, an individual must inherit two defective copies of the gene to develop severe deficiency, although even one altered copy can increase drug toxicity risk.
Risk Factors
Several factors increase the likelihood of complications related to the DPD gene mutation. The most significant risk factor is planned treatment with fluoropyrimidine chemotherapy drugs such as 5-Fluorouracil, Capecitabine, or Tegafur. Individuals undergoing cancer treatment are therefore at the highest risk.
A family history of severe chemotherapy reactions may also indicate an underlying genetic mutation. People with unexplained neurological symptoms, developmental delays, or previous adverse drug reactions may carry a partial enzyme deficiency. Since the mutation is inherited, having close relatives with known DPD deficiency increases personal risk.
Prevention
Prevention of complications related to the DPD gene mutation focuses on early detection and personalized treatment planning. Genetic or biochemical testing before starting fluoropyrimidine chemotherapy helps identify individuals at risk of severe toxicity. Testing allows clinicians to adjust drug dosage or select alternative treatments to avoid harmful reactions.
Avoiding standard doses of fluoropyrimidine drugs in patients with confirmed enzyme deficiency is critical. In cases of partial deficiency, careful dose reduction and close monitoring can significantly improve treatment safety. Awareness among healthcare providers and patients plays a key role in preventing life-threatening drug toxicity.
