Alpha-1 Antitrypsin Deficiency

Alpha-1 Antitrypsin Deficiency is a genetic condition that mainly affects the lungs and liver. It occurs when the body does not produce enough of a protein called alpha-1 antitrypsin, which protects the lungs from damage caused by enzymes. Without enough of this protein, harmful enzymes can attack lung tissue, leading to breathing problems like emphysema. The liver can also be affected because abnormal alpha-1 antitrypsin proteins can build up and cause liver damage. People with this condition may experience symptoms such as shortness of breath, wheezing, and chronic cough. It is important to understand that this condition is inherited and can vary in severity among individuals.

Alpha-1 Antitrypsin Deficiency is an autosomal codominant genetic disorder caused by mutations in the SERPINA1 gene leading to reduced serum levels or dysfunctional alpha-1 antitrypsin (AAT) protein. AAT is a protease inhibitor that primarily protects lung tissue from neutrophil elastase-mediated damage. Deficiency results in unchecked elastase activity causing early-onset panacinar emphysema, predominantly in the lower lung lobes. Additionally, misfolded AAT accumulates in hepatocytes causing liver disease ranging from neonatal hepatitis to cirrhosis and hepatocellular carcinoma. The most common pathogenic alleles are the Z and S variants, with the ZZ genotype conferring the highest risk. Clinical significance includes increased susceptibility to chronic obstructive pulmonary disease (COPD) in nonsmokers and smokers, and liver pathology due to intracellular AAT polymer accumulation.