Dihydropyrimidine dehydrogenase deficiency (DPD deficiency, also known as hereditary thymine-uraciluria) is an inherited disease that is caused by the absence of an enzyme called dihydropyrimidine dehydrogenase. This enzyme is needed for breaking down the molecules thymine and uracil, and also fluoropyrimidines, when present in the body.
For reasons that are not understood, most people with the genetic mutations that cause DPD deficiency have no symptoms at any time in their lives, while others are severely affected in infancy or childhood. Among those who are affected, about 50% have neurological symptoms including seizures, intellectual disability, and a delay in motor skills. Less common symptoms include autism, a small head, a delay in physical growth, eye abnormalities, and speech difficulties. These symptoms typically appear in infancy or childhood.
All people with DPD deficiency, regardless of the presence or absence of symptoms, cannot properly break down a class of drugs called fluoropyrimidines. Fluoropyrimidine is most commonly used as a chemotherapy agent (5-fluorouracil), but has also been used in ophthalmologic (eye) treatments and as a topical agent for dermatologic (skin) conditions. If given fluoropyrimidine drugs, individuals will have a severe toxic reaction that could be life-threatening. Signs of this reaction include diarrhea, swelling, digestive problems, muscle weakness, and an inability to coordinate muscle movement. Carriers of a mutation in the gene that causes this disease are also at risk for toxicity following treatment with fluoropyrimidines.
Though the severe presentation of this disorder is thought to be rare, the incidence of this condition is unknown because all variants are not associated with disease and many individuals are asymptomatic. Estimates of susceptibility to fluoropyrimidine toxicity are more readily available and one study showed that approximately 3% of Caucasians and 8% of African Americans are at risk for fluoropyrimidine toxicity.
There is no cure for DPD deficiency. Its symptoms can only be addressed as they arise (e.g. medication to prevent seizures). People with this disease must not take fluoropyrimidine drugs in order to avoid a toxic reaction.
For those who are asymptomatic, the prognosis is very good. Their lifespan should be unaffected by the disease. For those with more severe symptoms, it is unknown how these symptoms affect lifespan.
An article describing a case of hereditary thymine-uraciluria. The infant described has a genetic mutation associated with this disease--described here as the "G to A splice site mutation" or simply "splice site mutation." Note that the language in the article is scientific.