Alpha 1-atitrypsin deficiency: from genetic routes to bedside

Alpha 1-antitrypsin (A1AT) deficiency is a one of the most common genetic disorders in Caucasians. It is characterised by low serum levels of A1AT and a high risk of pulmonary emphysema and liver disease at a young age. The disease is caused by mutations in the SERPINA1 gene, which belongs to a cluster of protease inhibitor genes, with the main protein function of reducing the activity of serine-type endopeptidases, like neutrophil elastase. The most common mutation is E342K (Z), which is frequently found in northern Europeans. This mutation most probably arose in southern Sweden; however, the highest frequency of the Z mutation reported so far is in western Latvia. A1AT deficiency is not a widely recognised clinical problem. Disease onset most probably occurs in early adulthood with non-specific symptoms, like dyspnoea and recurrent pulmonary events, and it is triggered by certain risk factors, like smoking and working in an unfavourable environment.