Familial deficiency of dihydropyrimidine dehydrogenase. Biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity.

摘要: Severe neurotoxicity due to 5-fluorouracil (FUra) has previously been described in a patient with familial pyrimidinemia. We now report the biochemical basis for both pyrimidinemia and we have recently studied. After administration of "test" dose FUra (25 mg/m2, 600 microCi[6-3H]FUra by intravenous bolus) who had developed after FUra, markedly prolonged elimination half-life (159 min) was observed no evidence catabolites plasma or cerebrospinal fluid 89.7% administered being excreted into urine as unchanged FUra. Using sensitive assay dihydropyrimidine dehydrogenase peripheral blood mononuclear cells, demonstrated complete deficiency enzyme activity partial her father children consistent an autosomal recessive pattern inheritance. Patients are deficient this likely develop severe toxicity administration.