INHERITED METABOLIC LIVER-DISEASES

Modern techniques of molecular biology and genetics have had a major i mpact on the field of hepatology in general, and in the area of inheri ted metabolic diseases in particular. In the search for the responsibl e gene, investigation of hereditary hemochromatosis has moved from ped igree and linkage studies to newer techniques of positional cloning, i n the hope that the gene will soon be cloned and its products identifi ed. While this is awaited, population screening studies continue to pl ay a major role in case detection of this most common human genetic di sorder. Confirmation of diagnosis has been refined by precise use of t he hepatic iron index, while noninvasive techniques for the quantifica tion of iron stores by magnetic resonance imaging are being developed rapidly. Animal models for human genetic diseases are providing very u seful insights into pathophysiologic and molecular genetic aspects of these disorders. Such models are now available for hereditary hemochro matosis, alpha(1)-antitrypsin deficiency, and Wilson's disease. Finall y, 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 express ion of the disease.