Purpose of review: The past decade has seen extraordinary growth in our understanding of the pathophysiology of Wilson disease, genetic hemochromatosis and alpha-1 antitrypsin deficiency as we continue to elucidate the molecular and cellular machinery involved in their pathogenesis. The continued progress in the elaboration of the molecular biology, genetics, epidemiology, and management of these prototypical inherited metabolic diseases will be the focus of this review.
Recent findings: Wilson disease and genetic hemochromatosis involve defects in metal transport with copper and iron accumulation in hepatocytes, respectively. In alpha-1 antitrypsin deficiency, hepatocytes accumulate defective alpha-1 antitrypsin that misfolds. As a more complete picture of the molecular biology of the proteins and genes involved in transport has evolved, so has our understanding of the etiopathogenesis of these disorders and the variety of phenotypes observed. Finally, new ideas regarding the clinical management of these disorders will emerge with elucidation of the cellular basis for these diseases.
Summary: The recent developments detailed in this article have important implications for the future diagnosis and treatment of these diseases. Recent discoveries link molecular defects with alterations in the functional machinery of the cell, and provide new avenues for advancing the diagnosis and treatment of these disorders.