α1-antitrypsin deficiency

α1-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 α1 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 α1-antitrypsin deficiency arises in the SERPINA 1 gene and gives rise to the Z allele. This mutation reduces concentrations in serum of α1 antitrypsin by retaining polymerised molecules within hepatocytes: an amount below the serum protective threshold of 11 μmol/L increases risk for emphysema. In addition to the usual treatments for emphysema, infusion of purified α1 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.