J Inherit Metab Dis 1991;14(4):512-25

Alpha 1-antitrypsin deficiency and liver disease

Birrer P, McElvaney NG, Chang-Stroman LM, Crystal RG
Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes
of Health, Bethesda, Maryland 20892

Abstract
Alpha 1-antitrypsin (alpha 1AT) 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, alpha 1AT 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 alpha 1AT deficiency is not as well understood, but is clearly
linked to specific mutations in coding exons of the alpha 1AT gene, and the
resulting accumulation of alpha 1AT within hepatocytes. At present, therapy for
the liver disease associated with alpha 1AT deficiency is symptomatic, with
liver transplantation as a last resort. New strategies are being developed to
suppress the accumulation of alpha 1AT by transferring the normal gene into the
liver