II. Epidemiology
- Age of onset: 20 to 50 years
III. Pathophysiology
- Serpina1 gene defect (Chromosome 14q31-32.3) results in Alpha-1 Antitrypsin Deficiency
- Alpha-1 Antitrypsin protects against the Leukocyte enzyme Neutrophil elastase
- When Alpha-1 Antitrypsin is deficient, neutophil elastase results in tissue damage
- Lung alveolar damage (most common, resulting in pan-acinar Emphysema)
- Liver injury (less common)
- Skin Injury (rare)
IV. Presentations: Clinical manifestations that warrant screening
- Emphysema onset before age 45 years
- Emphysema without Tobacco exposure or occupational exposure
- Emphysema predominantly affecting the lower lung lobes
- Idiopathic Chronic Hepatitis
- Family History of COPD or Bronchiectasis at a young age or without risk factors
V. Labs
- Serum Alpha-1 Antitrypsin
- Deficiency: Level <1.5 g/L (<20 umol/L)
VI. Management
- See COPD Management
- Eliminate exacerbating exposures
- Avoid Tobacco exposure
- Avoid occupational exposures of airborne toxins
- Substitution therapy with human Alpha-1 Antitrypsin (Aralastin, Prolastin)
- Weekly injection of Alpha-1 Antitrypsin (60 mg/kg) from pooled human plasma
- Indicated in non-smokers, progressive COPD, and serum level <0.8 g/L (<11 umol/L)
VII. Complications
- Chronic Obstructive Pulmonary Disease (Emphysema)
- Neonatal Hepatitis
- Chronic Hepatitis (adults)
- Cirrhosis (and associated risk of Hepatocellular Carcinoma)
- Granulomatosis with Polyangiitis (previously known as Wegener's Granulomatosis, rare)
- Skin Necrotizing Panniculitis (rare)