Inherited Metabolic Liver Disease

Michael L Schilsky; Ioannis Oikonomou


Curr Opin Gastroenterol. 2005;21(3):275-282. 

In This Article

Abstract and Introduction

Purpose of Review: The purpose of this review is to identify and discuss recent findings related to inherited metabolic disorders of the liver that increase our understanding of the pathophysiology and treatment for hemochromatosis and other iron overload disorders, Wilson disease and alpha one antitrypsin deficiency.
Recent Findings: The main theme in the recent discoveries for both iron overload disorders and Wilson disease is our increasing understanding that the phenotypic expression of these disorders are greatly influenced by genes involved in the metabolic pathways for these metals, or influence the progression of liver disease independent of metal metabolism. For example, the role of hepcidin dysregulation in hemochromatosis has been a surprising discovery that provides some mechanistic understanding for the increased iron absorption that is present in this disorder.
Summary: Given the recent explosion of information on iron and copper metabolism and the cellular processing of alpha one antitrypsin, the highlights reviewed in this article will help the reader keep up to date with the current understanding of these diseases and potential future approaches to their treatment.

Recently we have identified novel proteins involved in metal metabolism and in cellular protein processing, and we are struggling now to understand how these discoveries are linked to the clinical expression of disease. This review focuses on genetic hemochromatosis and iron overload disorders, Wilson disease and alpha 1 antitrypsin deficiency. We now recognize that the phenotypic and clinical expression of these disorders is altered by many different genes not associated with the primary genetic defect for these diseases. Some of these are involved in metal or protein metabolism, while others are part of our global responses to oxidative injury and fibrogenesis. Clearly, our understanding of why these disorders present with a wide spectrum of phenotypic disease will continue to evolve. Elucidating the underlying basis for these differences will hopefully lead to interventions that may be useful in predicting and altering the natural history of these as well as other disorders.