alpha1-antitrypsin (alpha 1AT) deficiency is a common lethal hereditary dis
order of white persons of European descent. The condition is characterized
by reduced serum levels of alpha 1AT, a 52-kDa glycoprotein synthesized chi
efly in the liver and, to a lesser extent, by macrophages and neutrophils.
alpha 1AT acts as an antiprotease and is the physiological inhibitor of neu
trophil serine proteases such as neutrophil elastase cathepsin G and protei
nase 3. The clinical manifestations of alpha 1AT deficiency occur chiefly i
n the lung, with a high risk of emphysema occurring by the third or fourth
decade of life. Cigarette smoking accelerates the development of emphysema
in persons with alpha 1AT deficiency. There is also an increased risk of li
ver disease in alpha 1AT deficiency, which occurs mostly in childhood. In t
his review, we will define further the diagnosis of alpha 1AT deficiency an
d its clinical manifestations and describe the therapeutic strategies that
are currently being developed to treat the hepatic and pulmonary disease as
sociated with this condition.