α1-Antitrypsin (α1AT) deficiency, one of the most common lethal hereditary disorders among Caucasians, is associated with emphysema in adults, while in children it is associated with liver disease. Produced in the liver and released into the plasma, α1AT serves as the body's major inhibitor of neutrophil elastase, a powerful proteolytic enzyme capable of degrading extracellular structural proteins. The pathogenesis of the liver disease associated with α1AT deficiency is not as well understood, but is clearly linked to specific mutations in coding exons of the α1AT gene, and the resulting accumulation of α1AT within hepatocytes. At present, therapy for the liver disease associated with α1AT deficiency is symptomatic, with liver transplantation as a last resort. New strategies are being developed to suppress the accumulation of α1AT by transferring the normal gene into the liver.
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