Alpha-1 Antitrypsin Deficiency (Alpha-1 Proteinase Inhibitor Deficiency)

Alpha-1 Antitrypsin Deficiency (AATD) – Treatment Overview

Introduction
Alpha-1 antitrypsin deficiency (AATD), also called alpha-1 proteinase inhibitor deficiency, is a rare genetic disorder caused by mutations in the SERPINA1 gene that reduce or eliminate production of alpha-1 antitrypsin (AAT). AAT is a protease inhibitor that protects lung tissue from neutrophil elastase. Its deficiency leads to early-onset emphysema (COPD-like disease), liver disease (cirrhosis, hepatocellular carcinoma), and occasionally skin panniculitis. Management aims to slow lung damage, prevent complications, and improve quality of life.

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Treatment Options and Doses

1. General and Supportive Measures

• Smoking cessation: Most important step; smoking accelerates lung damage.

• Vaccinations: Annual influenza and pneumococcal vaccines.

• Bronchodilators & inhaled corticosteroids (ICS):

  • Salbutamol (Albuterol): 2 puffs (90–100 mcg) every 4–6 hours as needed.

  • ICS/LABA combinations (e.g., budesonide/formoterol) if persistent symptoms.

• Pulmonary rehabilitation: Exercise training and breathing techniques.

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2. Augmentation Therapy (Specific for AATD Lung Disease)

• Intravenous alpha-1 proteinase inhibitor replacement (for patients with emphysema and serum AAT levels <11 µM):

  • Dose: 60 mg/kg IV infusion once weekly.

  • Products: Prolastin-C, Zemaira, Aralast NP, Glassia.

  • Goal: Maintain serum AAT above protective threshold to slow lung function decline.

• Not effective for liver disease since the problem is accumulation of abnormal AAT in hepatocytes.

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3. Management of Liver Disease

• Monitoring: Regular liver function tests, ultrasound, and screening for hepatocellular carcinoma.

• Avoid hepatotoxic drugs (e.g., alcohol, high-dose acetaminophen).

• Liver transplantation: Definitive treatment for end-stage liver disease.

  • Also restores normal AAT production.

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4. Advanced Disease Interventions

• Oxygen therapy: For chronic hypoxemia.

• Lung transplantation: For end-stage emphysema with severe airflow limitation.

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5. Investigational / Emerging Therapies

• Gene therapy and RNA interference (RNAi) therapies under study.

• Small molecule chaperones being investigated to reduce liver accumulation of misfolded AAT.