Inherited metabolic liver diseases

Modern techniques of molecular biology and genetics have had a major impact on the field of hepatology in general, and in the area of inherited metabolic diseases in particular. In the search for the responsible gene, investigation of hereditary hemochromatosis has moved from pedigree and linkage studies to newer techniques of positional cloning, in the hope that the gene will soon be cloned and its products identified. While this is awaited, population screening studies continue to play a major role in case detection of this most common human genetic disorder. Confirmation of diagnosis has been refined by precise use of the hepatic iron index, while noninvasive techniques for the quantification of iron stores by magnetic resonance imaging are being developed rapidly. Animal models for human genetic diseases are providing very useful insights into pathophysiologic and molecular genetic aspects of these disorders. Such models are now available for hereditary hemochromatosis, α₁-antitrypsin deficiency, and Wilson's disease. Finally, this past year has seen the localization and cloning of the Wilson's disease gene, a discovery that will undoubtedly provide a means for the early genotypic detection and the prevention of phenotypic expression of the disease.