Detection of beta-ureidopropionase deficiency with HPLC-electrospray tandem mass spectrometry and confirmation of the defect at the enzyme level

The pyrimidine bases uracil and thymine are degraded via the consecutive ac tion of three enzymes to beta -alanine and beta -aminoisobutyric acid, resp ectively. To date, a number of patients have been described with a deficien cy of dihydropyrimidine dehydrogenase and dihydropyrimidinase, the first tw o enzymes of the pyrimidine degradation pathway. In this study, we demonstr ate that the first patient presenting with N-carbamyl-beta -amino aciduria, due to a deficiency of beta -ureidopropionase, was easily diagnosed at the metabolite level using HPLC-tandem mass spectrometry. Urinary analysis sho wed strongly elevated levels of N-carbamyl-beta -alanine and N-carbamyl-bet a -aminoisobutyric acid, with normal or moderately increased levels of the pyrimidine bases and the dihydropyrimidines, respectively. The deficiency o f beta -ureidopropionase was confirmed by measuring all three enzymes of th e pyrimidine degradation pathway. No activity of beta -ureidopropionase cou ld be detected in a liver biopsy of the patient, while a normal activity of dihydropyrimidine dehydrogenase and dihydropyrimidinase was present. Thus, HPLC-tandem mass specrometry proved to be a powerful tool for the initial diagnosis of patients with deficiency of beta -ureidopropionase.