Genetic Basis of Alpha-1 Antitrypsin Deficiency in Emphysema

Overview of Alpha-1 Antitrypsin and Its Role in Lung Protection

Alpha-1 Antitrypsin (AAT) is a protein synthesized by the liver that plays a crucial role in protecting lung tissues from enzymatic damage. Genetic mutations affecting the SERPINA1 gene result in AAT deficiency, leading to an increased risk of emphysema and chronic obstructive pulmonary disease (COPD).

Pathophysiology of Alpha-1 Antitrypsin Deficiency

AAT functions by inhibiting neutrophil elastase, an enzyme that degrades lung connective tissue. Genetic mutations cause reduced AAT levels or misfolded proteins that accumulate in hepatocytes, preventing proper lung protection.

Clinical Manifestations

• Early-onset emphysema
• Shortness of breath
• Liver disease (cirrhosis)

Diagnosis and Genetic Testing

Diagnosis involves serum AAT levels, genetic testing for SERPINA1 mutations, and pulmonary function tests. Family screening is recommended due to its hereditary nature.

Treatment and Management

Management includes AAT augmentation therapy, bronchodilators, smoking cessation, and lung transplantation for severe cases.