Alpha-1-antitrypsin deficiency: diagnosis and treatment

Alpha-1-antitrypsin (AT) deficiency was first described in the late 1960s in patients with severe pulmonary emphysema. The recognition of AT deficiency as a cause of emphysema then led to what is still the prevailing theory for the pathogenesis of emphysema, the protease-antiprotease theory. Soon it was found that AT deficiency accounted for a significant number of cases of neonatal liver disease that were previously categorized as idiopathic. We now know that AT deficiency is the most common genetic cause of neonatal liver disease and the most frequent diagnosis necessitating liver transplantation. It has also been shown to cause chronic liver disease, cryptogenic cirrhosis, and hepatocellular carcinoma in adults never previously known to have liver disease in infancy or childhood. Observations indicate that genetic traits unlinked to the AT gene or environmental factors predispose to or protect AT-deficient individuals from liver disease.