Alpha-1-Antitrypsin Deficiency

1. Epidemiology
   1. Age of onset: 20 to 50 years
2. Pathophysiology
   1. Serpina1 gene defect (chromosome 14q31-32.3) results in Alpha-1 antitrypsin deficiency
   2. Alpha-1 antitrypsin protects against the Leukocyte enzyme Neutrophil elastase
   3. When Alpha-1 antitrypsin is deficient, neutophil elastase results in tissue damage
      1. Lung alveolar damage (most common)
      2. Liver injury (less common)
      3. Skin Injury (rare)
3. Presentations: Clinical manifestations that warrant screening
   1. Emphysema onset before age 45 years
   2. Emphysema without Tobacco exposure or occupational exposure
   3. Emphysema predominantly affecting the lower lung lobes
   4. Idiopathic Chronic Hepatitis
   5. Family History of COPD or Bronchiectasis at a young age or without risk factors
4. Labs
   1. Serum alpha-1 antitrypsin
      1. Deficiency: Level <1.5 g/L (<20 umol/L)
5. Management
   1. See COPD Management
   2. Eliminate exacerbating exposures
      1. Avoid Tobacco exposure
      2. Avoid occupational exposures of airborne toxins
   3. Substitution therapy with human alpha-1 antitrypsin
      1. Weekly injection of alpha-1-antitrypsin (60 mg/kg) from pooled human plasma
      2. Indicated in non-smokers, progressive COPD, and serum level <0.8 g/L (<11 umol/L)
6. Complications
   1. Chronic Obstructive Pulmonary Disease (Emphysema)
   2. Neonatal Hepatitis
   3. Chronic Hepatitis (adults)
   4. Cirrhosis (and associated risk of Hepatocellular Carcinoma)
   5. Wegener's Granulomatosis (rare)
   6. Skin Necrotizing Panniculitis (rare)
7. References
   1. Kohnlein (2008) Am J Med 121:3-9