Detection of β-ureidopropionase deficiency with HPLC–electrospray tandem mass spectrometry and confirmation of the defect at the enzyme level
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The 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.
KeywordsPyrimidine Liver Biopsy Tandem Mass Tandem Mass Spectrometry Uracil
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