Hereditary thymine-uraciluria is an inherited disease that can cause serious mental and physical delays in children. For reasons that are not understood, most people with the genetic mutations that cause hereditary thymine-uraciluria 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, mental 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 hereditary thymine-uraciluria, regardless of the presence or absence of symptoms, cannot properly break down the common chemotherapy drug 5-fluorouracil. If given this drug, they 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 5-fluorouracil treatment.
Hereditary thymine-uraciluria is caused by the absence of an enzyme called dihydropyrimidine dehydrogenase which is needed for breaking down the molecules thymine and uracil, and also 5-fluorouracil when it is present in the body.
Studies have shown that about 1% of Caucasians are carriers for a particular mutation that causes hereditary thymine-uraciluria. This mutation is common among people in the Netherlands, Finland, and Taiwan. Due to this mutation and other mutations in the same gene, an estimated 3% of Caucasians and 8% of African Americans are at risk for 5-fluorouracil toxicity.
There is no cure for hereditary thymine-uraciluria. Its symptoms can only be addressed as they arise (i.e. medication to prevent seizures). People with this disease must not take the drug 5-fluorouracil 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.