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Media type:
E-Article
Title:
Detection of β‐ureidopropionase deficiency with HPLC–electrospray tandem mass spectrometry and confirmation of the defect at the enzyme level
Contributor:
Van Kuilenburg, A. B. P.;
Van Lenthe, H.;
Assmann, B.;
Göhlich‐Ratmann, G.;
Hoffmann, G. F.;
Bräutigam, C.;
Wevers, R. A.;
Van Gennip, A. H.
Published:
Wiley, 2001
Published in:
Journal of Inherited Metabolic Disease, 24 (2001) 7, Seite 725-732
Description:
AbstractThe pyrimidine bases uracil and thymine are degraded via the consecutive action of three enzymes to β‐alanine and β‐aminoisobutyric acid, respectively. To date, a number of patients have been described with a deficiency of dihydropyrimidine dehydrogenase and dihydropyrimidinase, the first two enzymes of the pyrimidine degradation pathway. In this study, we demonstrate that the first patient presenting with N‐carbamyl‐β‐amino aciduria, due to a deficiency of β‐ureidopropionase, was easily diagnosed at the metabolite level using HPLC–tandem mass spectrometry. Urinary analysis showed strongly elevated levels of N‐carbamyl‐β‐alanine and N‐carbamyl‐β‐aminoisobutyric acid, with normal or moderately increased levels of the pyrimidine bases and the dihydropyrimidines, respectively. The deficiency of β‐ureidopropionase was confirmed by measuring all three enzymes of the pyrimidine degradation pathway. No activity of β‐ureidopropionase could 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 β‐ureidopropionase.