Inherited metabolic liver disease.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Schilsky
Michael L
ML
Center for Liver Disease and Transplantation, Division of Gastroenterology and Hepatology, New York Weill Cornell Medical Center, New York, USA. mls2003@med.cornell.edu
Fink
Scott
S
D000251:Adenosine Triphosphatases / Q000235:genetics; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics; D003300:Copper / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D000071020:Hemochromatosis Protein; D006527:Hepatolenticular Degeneration / Q000235:genetics* / Q000378:metabolism; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D019190:Iron Overload / Q000235:genetics* / Q000628:therapy; D008099:Liver / Q000503:physiopathology; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D019896:alpha 1-Antitrypsin Deficiency / Q000235:genetics* / Q000503:physiopathology
D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases