What is the pathophysiology of alpha1-antitrypsin deficiency (AATD)?

Updated: Sep 11, 2020
  • Author: Dora E Izaguirre Anariba, MD, MPH; Chief Editor: John J Oppenheimer, MD  more...
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Alpha1-antitrypsin deficiency (AATD) is a genetically inherited autosomal-codominant condition with more than 120 alleles identified. [1, 2] Alpha1-antitrypsin is the prototype member of the serine protease inhibitor (serpin) superfamily of proteins. AATD is caused by mutations in the SERPINA1 gene located in the long arm of chromosome 14. [1, 2, 5]  This genetic defect alters the configuration of the alpha1-antitrypsin molecule and prevents its release from hepatocytes. As a result, serum levels of alpha1-antitrypsin are decreased, leading to low alveolar concentrations, where the alpha1-antitrypsin molecule normally would serve as protection against proteases such as neutrophil elastase. The resulting protease excess in alveoli destroys alveolar walls and causes emphysema. Likewise, the accumulation of excess alpha1-antitrypsin in hepatocytes can also lead to destruction of these cells and ultimately, clinical liver disease.

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