alpha 1-antitrypsin deficiency: Biological answers to clinical questions

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.