Inherited metabolic liver disease

PURPOSE OF REVIEW: The past decade has seen understanding of the molecular machinery involved in the pathogenesis of genetic hemochromatosis, Wilson's disease, and alpha1-antitrypsin deficiency grow significantly. This year has seen further progress in elaborating the molecular biology, genetics, epidemiology, and management of these inherited metabolic diseases. RECENT FINDINGS: Both Wilson's disease and genetic hemochromatosis involve defects in the transport of heavy metals and their accumulation in hepatocytes. In alpha1-antitrypsin deficiency, intrahepatocyte accumulation of defective alpha(1)-antitrypsin occurs. As a more complete picture of the molecular biology of proteins and genes involved in transport has evolved, so has our understanding of their interactions. The molecular genetics of these diseases explains the different phenotypes seen. Finally, the elucidation of the molecular pathophysiology of these diseases has led to new ideas in their clinical management. SUMMARY: The recent developments detailed in this article have important implications for the future. Recent research has elegantly shifted the paradigm in our understanding to one focused on defects in the genetic machinery of the cell and on how better comprehension of these defects can lead to potential new therapies.