Alpha-1 antitrypsin deficiency is an autosomal codominant disease caused by mutations in the SERPINA1 gene. A1AD affects 1:1,500-3,000 individuals of European descent, and it is considered a significantly underdiagnosed disease. The resulting decrease or dysfunction of this protein, whose main function is enzyme inhibition of proteases released by inflammatory cells, leads to tissue damage. The most common clinical manifestation is lung damage (emphysema, bronchiectasis, and COPD), followed by liver involvement (chronic hepatitis, liver cirrhosis, and hepatocarcinoma) and, less frequently, vasculitis, panniculitis, inflammatory bowel disease, intracranial and abdominal aneurysms, fibromuscular dysplasia, and glomerulonephritis.
At least 150 alleles associated with A1AD have been described throughout the whole gene. In clinical practice, the risk of developing the disease is associated with ZZ phenotypes in 96% of cases, while the remaining 4% is associated with rare variants of this deficiency, generally known as M-like and S-like, and with extremely rare null genotypes. Up to 60% of ZZ individuals can develop chronic airway obstruction, smoking being the main risk factor associated with this outcome.