Usefulness of uracil loading test for detecting 5-fluorouracil metabolic enzyme deficiencies in humans

Background. We investigated the usefulness of the uracil loading test to detect human carriers of dihydropyrimidine dehydrogenase (DPD) and dihydropyrimidinase (DHPase) deficiencies. Methods. Our subjects consisted of family A (including a patient, a 37-year-old man with a urinary dihydrouracil (DHU) level of 185.4 μmol/mmol creatinine [Cre]); family B (including a patient, a 3-month-old girl with a DHU level of 154.3 μmol/mmol Cre); and ten healthy volunteers. Oral loading tests were performed with 10 mg/kg of uracil to examine changes in the serum and urinary levels of uracil and dihydrouracil in the subjects. Results. The uracil loading test showed the highest levels of urinary DHU 120 min after loading in the mother and father of the patient in family A (52.2 and 65.4 μmol/mmol Cre, respectively) and the mother of the patient in family B (66.4 μmol/mmol Cre). Conclusion. These urinary DHU levels were higher than those in the ten healthy adults, which led us to diagnose these individuals with high DHU levels as human carriers of DHPase deficiencies.[PUBLICATION ABSTRACT]