DIHYDROPYRIMIDINASE DEFICIENCY PRESENTING IN INFANCY WITH SEVERE DEVELOPMENTAL DELAY

Dihydropyrimidinase (5,6-dihydropyrimidine amidohydrolase; EC 3.5.2.2), is the second enzyme involved in the breakdown of the pyrimidine bases uracil and thymine and catalyses the degradation of both dihydrouracil and dihydrothymine to beta-ureidopropionic acid and beta-ureidoisobutyric acid, respectively. The first case of dihydropyrimidinuria in humans was reported recently in an infant presenting with convulsions but whose subsequent development had been normal (Duran et al 1991). A deficiency of dihydropyrimidinase was assumed from the excretion in the urine of the substrates for the enzyme, dihydrouracil and dihydrothymine. One other defect of the pyrimidine catabolic pathway had been described previously in patients with a variety of neurological abnormalities (Brockstedt et al 1990). This was a defect of the preceeding enzyme, dihydropyrimidine dehydrogenase (DPDH). This short report describes dihydropyrimidinuria in a child who presented at 6 weeks with seizures and had gross neurological deficit at 2 1/2 years of age.