Alpha1-antitrypsin deficiency (AATD) is caused by a mutation in the SERPINA1 gene. SERPINA1 is located on chromosome 14.

• Alpha1-antitrypsin deficiency (AATD) is caused by a mutation in the SERPINA1 gene.^[1][2]
• SERPINA1 is located on chromosome 14 and is highly pleomorphic, with more than 100 allelic variants.This gene instructs the body to make a protein called alpha-1 antitrypsin (AAT), which functions to inhibit neutrophil elastase enzyme.
• Neutrophil elastase helps the body fight infections, but it can also attack healthy tissue in the lung if not inactivated by AAT. Alpha1-antiprotease functions to protect the lungs from unregulated protease activity.
• Mutations associated with AAT can result in:
  • Deficient amount of AAT in the body.
  • Complete absence of AAT.
  • A form of AAT that does not work effectively to protect healthy lung tissue.
• SERPINA1 mutation allows neutrophil elastase to destroy lung tissue, causing lung disease.
• In addition, the accumulation of intrahepatic alpha1-antitrypsin can build up in the liver and can result in apoptosis of hepatocytes.
• The severity of AATD may also be worsened by environmental factors such as exposure to tobacco smoke, dust, and chemicals. This initially presents as laboratory abnormalities on liver function test, but can progress to hepatitis, followed by fibrosis and cirrhosis.

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