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Pulmonary & Respiratory

Alpha-1 Antitrypsin Deficiency

Affects approximately
1 in 2,500 to 3,500 people; affects approximately 100,000 Americans

Also known as: Alpha-1, AAT deficiency, AATD

Alpha-1 Antitrypsin Deficiency

About Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency (AATD) is an autosomal recessive genetic disorder affecting alpha-1 antitrypsin (AAT) production, a protease inhibitor that protects lung tissue from neutrophil elastase-mediated damage. Individuals with severe AAT deficiency (PiZZ genotype) have AAT levels less than 15% of normal, insufficient to protect against lung damage. Without protection, neutrophil elastase damages the elastic fibers of the lung, causing emphysema typically in lower lung lobes (in contrast to smoking-related emphysema in upper lobes). Symptoms typically appear in the fourth to fifth decade in smokers; non-smokers may remain asymptomatic or develop disease later. Liver disease occurs in some patients due to accumulation of abnormal AAT polymers in hepatocytes. The combination of AAT deficiency and smoking dramatically accelerates lung disease progression.

Common Symptoms

  • Early-onset emphysema and chronic obstructive pulmonary disease (COPD)
  • Shortness of breath with exertion
  • Chronic cough
  • Liver disease ranging from neonatal cholestasis to cirrhosis
  • Liver failure in severe cases
  • Accelerated lung disease in smokers with AAT deficiency

Who It Affects

Early-onset emphysema typically appears ages 40-60 in smokers; non-smokers often have later onset or milder disease. Autosomal recessive inheritance; higher prevalence in people of Northern European descent. About 25 million people in the U.S. are carriers.

Getting Involved in Clinical Trials

Alpha-1 augmentation therapy (infusions of AAT) can stabilize lung function and slow progression in some patients. Clinical trials are evaluating new augmentation therapies, gene therapy approaches, and small-molecule therapies to increase endogenous AAT production. The Alpha-1 Foundation and patient organizations provide information on treatments and trials. All individuals with symptomatic lung disease should be tested for AAT deficiency. Family screening is important, as carriers and affected individuals benefit from early intervention and smoking cessation. Augmentation therapy should be considered for individuals with severe AAT deficiency and evidence of progressive lung disease.

Trusted Sources

Active Clinical Trials for Alpha-1 Antitrypsin Deficiency

Finding trials for Alpha-1 Antitrypsin Deficiency...

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