Journal of Inherited Metabolic Disease

, Volume 14, Issue 4, pp 563–579 | Cite as

Investigation of the molecular basis of the genetic deficiency of UDP-glucuronosyl-transferase in Crigler-Najjar syndrome

  • K. J. Robertson
  • D. Clarke
  • L. Sutherland
  • R. Wooster
  • M. W. H. Coughtrie
  • B. Burchell
Article

Summary

Liver biopsy samples were obtained from eight Crigler-Najjar patients. Bilirubin UDPGT activity, assayed by a microassay with HPLC analysis, was not detectable in type I livers, and low levels (9–26% of controls) of monoglucuronide conjugates only were observed in type II livers. 1-Naphthol UDPGT activity was normal in most patients, where membrane integrity was maintained by correct sample procurement and preparation. Our data on type II livers suggest that a defect in UDPGA transport is an unlikely cause of the hyperbilirubinaemia, but reduced affinity for UDPGA was observed in one sample. Analysis of four patient liver samples by immunoblot analysis revealed the heterogeneous nature of this inherited disease within the patient population, and one sample where 1-naphthol UDPGT activity was considerably reduced appeared to correlate with the non-detection of a phenol UDPGT protein. Progress towards a molecular genetic diagnosis of Crigler-Najjar syndromes is discussed.

Keywords

Phenol Bilirubin Molecular Basis Liver Biopsy HPLC Analysis 

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Copyright information

© SSIEM and Kluwer Academic Publishers 1991

Authors and Affiliations

  • K. J. Robertson
    • 1
  • D. Clarke
    • 1
  • L. Sutherland
    • 1
  • R. Wooster
    • 1
  • M. W. H. Coughtrie
    • 1
  • B. Burchell
    • 1
  1. 1.Department of Biochemical Medicine, Ninewells Hospital and Medical SchoolUniversity of DundeeDundeeUK

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