Inherited metabolic liver disease.

PURPOSE OF REVIEW: The following section focuses on the disorders Wilson disease hemochromatosis and alpha-one antitrypsin deficiency, and the pivotal findings in publications this past year that furthers our understanding of the pathophysiology and treatment of these disorders.

RECENT FINDINGS: For Wilson disease, there is new data regarding the structure and function of the responsible protein, ATP7B, and the importance of its proper cellular localization in hepatocytes, Other new information regarding the further use of zinc for initial treatment of this disease for asymptomatic patients, and the initial use of tetrathiomolybdate for neurologically affected patients will change our future approach to the treatment of patients with this disorder. New guidelines for diagnosis and treatment have also been set forth. New data has also advanced our understanding of hemochromatosis and iron overload disorders. Highlights this year include the discovery of a new gene involved in iron metabolism, hemojuvelin, and new data on the role of HFE mutations in the development of iron overload. Other data suggests that the altered regulation of the peptide hepcidin may play a pivotal role in the development of the iron overload phenotype in patients with hemochromatosis. For alpha-one antitrypsin, new information on the incidence of the disease in African based populations is being collected, and the role of autophagy in the pathogenesis of the disease continues to be explored.

SUMMARY: Further understanding of these physiological alterations will help to better our understanding of the development of iron overload disorders, and may offer new avenues for therapeutic intervention.