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Journal of Inherited Metabolic Disease

, Volume 24, Issue 7, pp 725–732 | Cite as

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

  • A. B. P. Van Kuilenburg
  • H. Van Lenthe
  • B. Assmann
  • G. Göhlich-Ratmann
  • G. F. Hoffmann
  • C. Bräutigam
  • R. A. Wevers
  • A. H. Van Gennip
Article

Abstract

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.

Keywords

Pyrimidine Liver Biopsy Tandem Mass Tandem Mass Spectrometry Uracil 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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REFERENCES

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Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • A. B. P. Van Kuilenburg
    • 1
    • 2
    • 3
  • H. Van Lenthe
    • 1
    • 2
    • 3
  • B. Assmann
    • 4
  • G. Göhlich-Ratmann
    • 5
  • G. F. Hoffmann
    • 4
  • C. Bräutigam
    • 4
  • R. A. Wevers
    • 6
  • A. H. Van Gennip
    • 1
    • 2
    • 3
  1. 1.Academic Medical CenterUniversity of AmsterdamThe Netherlands
  2. 2.Emma Children's HospitalThe Netherlands
  3. 3.Department of Clinical ChemistryThe Netherlands
  4. 4.Department of PediatricsUniversity Hospital HeidelbergHeidelbergGermany
  5. 5.Department of PediatricsUniversity Hospital EssenEssenGermany
  6. 6.University Hospital NijmegenThe Netherlands

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