Genetic Basis of Alpha-1 Antitrypsin Deficiency in Emphysema

Alpha-1 Antitrypsin (AAT) deficiency is a genetic disorder that leads to an increased risk of developing emphysema due to the unregulated activity of neutrophil elastase in the lungs. AAT, a serine protease inhibitor produced by the liver, plays a crucial role in protecting lung tissue from enzymatic degradation.

Genetic Background

The SERPINA1 gene encodes Alpha-1 Antitrypsin, and mutations in this gene result in reduced or dysfunctional protein production. The most common mutations associated with severe deficiency are the Z and S alleles.

Pathophysiology and Pulmonary Impact

• Loss of Protease Inhibition: Deficiency leads to excessive neutrophil elastase activity, causing degradation of elastin in alveolar walls.
• Emphysematous Changes: Progressive destruction of alveoli results in impaired gas exchange and reduced lung function.
• Inflammatory Cascade: Chronic inflammation further accelerates pulmonary damage.

Clinical Presentation and Management

Patients with AAT deficiency may present with early-onset emphysema, dyspnea, and increased susceptibility to pulmonary infections. Management strategies include augmentation therapy with exogenous AAT, bronchodilators, and smoking cessation.