Authors: Michael Kaplan; Cathy Hammerman

Source: Current Pharmacogenomics, Volume 3, Number 1, March 2005 , pp. 21-42(22)

Publisher: Bentham Science Publishers

Abstract:

Severe neonatal unconjugated hyperbilirubinemia, with the risk of bilirubin encephalopathy or kernicterus in severe, untreated cases, occurs when bilirubin production exceeds the body's ability to eliminate it. The causes of neonatal hyperbilirubinemia are multifactorial and comprise increased hemolysis on the one hand, and diminished bilirubin conjugation on the other. In recent years, many of these etiologies have been found to have a genetic origin. Sometimes hereditary factors act independently, but in other circumstances, single mutations which ordinarily do not produce disease in and of themselves, may result in severe hyperbilirubinemia as a result of interaction with other mutated genes. Of cardinal importance to this discussion is the concept of the human genome, whereby the thousands of genes of which it is comprised may interact one with the other, or with the environment, exacerbating the severity of jaundice in certain individuals, and protecting against hyperbilirubinemia in others. Genetic interactions have been demonstrated combining increased bilirubin production with diminished bilirubin conjugation, resulting in severe hyperbilirubinemia. Appreciation of the multiplicity of genetic interactions is of importance in our evaluation of the neonate with severe hyperbilirubinemia, in our attempts to prevent future cases of kernicterus, and in genetic counseling of families who have had an infant with severe neonatal hyperbilirubinemia. Gene therapy for the most severe of these inherited defects of bilirubin conjugation, Crigler-Najjar syndrome type 1, might become a reality in future years.

Keywords: jaundice; serum total bilirubin; blood-brain barrier; kernicterus; production-conjugation index; metabolism

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1570160053174992

Affiliations: 1: Department of Neonatology, Shaare Zedek Medical Center, PO Box 3235, Jerusalem 91031, Israel.

Publication date: 2005-03-01

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• Current Pharmacogenomics provides comprehensive overviews of all current research on pharmacogenomics and pharmacogenetics. All areas of the field from pre-clinical to clinical research are covered, including related areas such as genomics, proteomics, target discovery, bioinformatics and novel diagnostics. This international journal is peer-reviewed and publishes both mini- and full review articles.
  
  The journal has become essential reading for all researchers and clinicians with interests in pharmacogenomics and pharmacogenetics.

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