Overview
Definition
An autosomal recessive genetic disorder affecting the CFTR protein, resulting in the production of thick, viscous mucus that damages the lungs, digestive system, and other organs.
Epidemiology
Most common life-limiting genetic disease in Caucasians. Median survival is now > 50 years with new therapies.
Etiology & Risk Factors
- Mutation in the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene on chromosome 7
- The most common mutation is F508del (deletion of phenylalanine at position 508)
- Defective chloride channel leads to impaired sodium/water transport across epithelial cells
Clinical Symptoms
- Respiratory: Chronic cough with thick sputum, recurrent pulmonary infections, hemoptysis
- GI: Meconium ileus (in neonates), Pancreatic insufficiency (steatorrhea, malabsorption), Failure to thrive
- Other: Salty-tasting skin, male infertility (congenital bilateral absence of the vas deferens - CBAVD)
Clinical Approach
Diagnosis
- Newborn screening (Elevated Immunoreactive Trypsinogen - IRT)
- Sweat Chloride Test (Gold Standard): Chloride ≥ 60 mmol/L on two occasions
- CFTR mutation genetic testing
Management
- Airway clearance techniques (Chest physiotherapy, hypertonic saline, Dornase alfa)
- Antibiotics for exacerbations (must cover Pseudomonas aeruginosa and Staph aureus)
- Pancreatic enzyme replacement therapy (PERT) and fat-soluble vitamin supplementation (ADEK)
- CFTR Modulators (e.g., Elexacaftor/Tezacaftor/Ivacaftor - 'Trikafta') - game-changing therapy for patients with specific mutations like F508del
- Lung transplantation (for end-stage lung disease)
Complications
- Bronchiectasis
- Chronic respiratory failure
- CF-related diabetes
- Cirrhosis / Biliary disease