Alpha-1-Antitrypsin Deficiency

Abstract

A relationship between the development of emphysema and low serum levels of alpha-1-antitrypsin (AAT) was first noted in 1963 by Laurell and Eriksson [1]. A few years later, Sharp et al. [2] reported liver damage in AAT deficiency (AATD) AAT, also referred to as α_l-protease inhibitor or protein inhibitor (PI), is a 52-kDa glycoprotein synthesized in the liver and secreted into plasma, where it accounts for 90% of serum α₁-globulin. Although inhibitory of trypsin (hence its name), the major function of AAT is to inhibit neutrophil elastase at inflammation sites, e.g., within the alveoles. Whereas normal AAT (termed M) readily diffuses throughout interstitial fluids, the defective molecules formed in AATD aggregate inside the hepatocytes, resulting in poor secretion into blood and the fluids of the respiratory tract. Several defective variants of AAT have been identified, of which the most frequently encountered is Z.