α1-antitrypsin deficiency

alpha 1-antitrypsin deficiency is a genetic disorder that affects about one in 2000-5000 individuals. It is clinically characterised by liver disease and early-onset emphysema. Although alpha 1 antitrypsin is mainly produced in the liver, its main function is to protect the lung against proteolytic damage from neutrophil elastase. The most frequent mutation that causes severe alpha 1-antitrypsin deficiency arises in the SERPINA1 gene and gives rise to the Zallele. This mutation reduces concentrations in serum of alpha 1 antitrypsin by retaining polymerised molecules within hepatocytes: an amount below the serum protective threshold of 11 mu mol/L increases risk for emphysema. In addition to the usual treatments for emphysema, infusion of purified alpha 1 antitrypsin from pooled human plasma represents a specific treatment and raises the concentrations in serum and epithelial-lining fluid above the protective threshold. Evidence suggests that this approach is safe, slows the decline of lung function, could reduce infection rates, and might enhance survival. However, uncertainty about the cost-effectiveness of this expensive treatment remains.