Alpha-1 Proteinase Inhibitor Deficiency

Alpha-1 Proteinase Inhibitor Deficiency – Treatment Overview

Introduction
Alpha-1 proteinase inhibitor deficiency (commonly called Alpha-1 antitrypsin deficiency, AATD) is a hereditary disorder caused by mutations in the SERPINA1 gene, leading to low or dysfunctional levels of alpha-1 proteinase inhibitor (AAT). AAT normally protects lung tissue from proteolytic damage by neutrophil elastase. Deficiency predisposes patients to early-onset emphysema/COPD, chronic bronchitis, and bronchiectasis, as well as liver disease due to accumulation of abnormal AAT within hepatocytes. Less commonly, it may cause necrotizing panniculitis. Management aims to prevent lung damage, monitor and treat liver complications, and in selected cases provide augmentation therapy.

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Treatment Options and Doses

1. General Supportive Measures

• Smoking cessation: Absolute priority – smoking markedly accelerates emphysema.

• Vaccination: Influenza annually, pneumococcal vaccine every 5–10 years, and hepatitis A/B vaccines for those with liver involvement.

• Lifestyle: Avoid dust, fumes, alcohol (if liver affected), and hepatotoxic medications.

• Pulmonary rehabilitation: Improves exercise capacity and quality of life.

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2. Pharmacologic Symptom Control (COPD-like management)

• Bronchodilators:

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

  • Tiotropium (LAMA): 18 mcg inhaled once daily.

• Inhaled corticosteroids (ICS) + LABA (if indicated):

  • Budesonide/Formoterol 160/4.5 mcg: 2 inhalations twice daily.

• Oxygen therapy: For chronic hypoxemia (PaO₂ ≤55 mmHg).

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3. Augmentation Therapy (Specific for AATD Lung Disease)

• Indication: Non-smoking patients with confirmed AATD, emphysema, and serum AAT levels <11 µM.

• IV AAT infusion (human plasma–derived):

  • Dose: 60 mg/kg intravenously once weekly.

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

• Shown to slow decline in lung function (FEV1) but does not reverse existing damage.

• Not beneficial for liver disease.

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4. Management of Liver Disease

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

• Lifestyle: Absolute avoidance of alcohol, weight management, and hepatitis vaccination.

• Liver transplantation: Definitive treatment for cirrhosis or end-stage liver failure.

  • Transplant restores normal AAT production and cures liver disease.

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5. Advanced/Curative Options

• Lung transplantation: For end-stage emphysema unresponsive to medical therapy.

• Experimental therapies: Gene therapy, RNA-based therapies, and small-molecule chaperones are under study to address both lung and liver pathology.