Dihydropyrimidine dehydrogenase deficiency is a condition that varies widely in its impact. Some individuals experience neurological issues, while others show no signs of the disorder.
In severe cases of this deficiency, problems emerge in infancy. These individuals may have seizures, intellectual disability, small head size, muscle stiffness, delayed motor skills development, and challenges in communication and social interaction (autistic behaviors). On the other hand, some people don’t display any symptoms and are only identified through laboratory tests. Regardless of symptoms, individuals with this deficiency face a significant risk when exposed to certain cancer drugs like 5-fluorouracil and capecitabine. These drugs aren’t efficiently broken down in their bodies and accumulate to harmful levels, causing toxic reactions. These reactions may lead to severe inflammation and ulceration in the gastrointestinal tract, resulting in issues like mouth sores, abdominal pain, bleeding, nausea, vomiting, and diarrhea. Moreover, the toxicity can lower white blood cell counts, increasing the risk of infections, and reduce platelet numbers, affecting blood clotting and potentially causing abnormal bleeding. Other side effects may include skin problems, shortness of breath, and hair loss.
Dihydropyrimidine dehydrogenase deficiency is caused by pathogenic (disease-causing) variants in the DPYD gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background.
Carriers may still experience toxic reactions to fluoropyrimidine drugs.
Other names for this condition are dihydropyrimidinuria, familial pyrimidemia, and hereditary thymine-uraciluria.
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Revised October 2023
