Alpha-1 antitrypsin deficiency: diagnosis and treatment

Alpha-1 antitrypsin (AAT) deficiency (D) is an autosomic codominant genetic condition associated with an increased risk of lung and liver disease. Lung disease is usually seen as an emphysema developing during the 4(th) or 5(th) decade, that may be associated with disseminated bronchiectasis, or it may be more similar to a COPD or, more rarely, to asthma. Liver disease can be seen within the first year of life as hepatic cholestasis, or later on during the 5(th) or 6(th) decade as a chronic hepatic disorder or liver cirrhosis or even hepatic cancer. Gene-environment interaction is crucial in AATD associated clinical manifestations. The risk of lung diseases is increased manifold in smokers. Life-long non smokers can be asymptomatic and without any evidence of lung disease for the whole life. Diagnosis is based on the determination of AAT plasma levels followed, in the case of values lower than normal, by genotyping. Pharmacological treatment of lung disease (COPD) associated with AATD comprises AAT replacement therapy, i.e. a weekly i.v. infusion of AAT from the blood donor pool. Replacement therapy is considered able to slow the annual decline of lung function, particularly accelerated in AATD. Pulmonary rehabilitation, lung or liver transplantation are the other non-pharmacological options in the management of AATD associated diseases.