Cystic Fibrosis: An Overview

Genetic Basis

• Inherited disorder characterized by defective CFTR gene.
• Autosomal recessive inheritance.
  • Both parents must carry faulty gene.
• 1 in 25 Caucasian people are carriers.
• Median survival age as of 2021: 33.9 years.
• Projected survival for those born 2018-2022: 56 years.

CFTR Gene and Protein

• Located on Chromosome 7.
• Codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein.
  • Forms chloride channel that regulates ion movement.
• Over 2,000 variants; 85% of cases due to f508 deletion.

Impact on Organs

• Lungs: Thick mucus causes infections, inflammation, and bronchiectasis.
• Pancreas: Obstruction leads to enzyme activation and autodestruction.
• Liver: Biliary damage leads to fibrosis and possibly cirrhosis.
• Intestines: Viscous secretions cause obstructions, especially in neonates.
• Reproductive System:
  • Males: 98% infertility due to vas deferens issues.
  • Females: Fertility issues due to viscous cervical mucus.

Clinical Manifestations

• Symptoms begin in infancy or childhood.
• Respiratory: Recurrent infections, coughing, wheezing, breathlessness.
• Digestive: Malabsorption, poor growth, foul-smelling stools.
• Other: Salty skin, dehydration risk.

Diagnosis

• Often identified via newborn screening.
• Sweat test measures chloride concentration in sweat.
  • Normal: <30 mmol/L; Abnormal: >60 mmol/L.
• Genetic testing to confirm CFTR variants.

Treatment and Management

• Respiratory: Vaccines, airway clearance, aerobic exercise.
• Medications:
  • CFTR modulators (e.g., Ivacaftor, Lumacaftor).
  • Antibiotics for infections and prophylaxis.
  • Bronchodilators and mucolytics.
• Nutritional Support: High-calorie diet, enzyme replacement.
• Surgery: In severe cases (e.g., lung transplantation).

Complications

• Frequent infections and respiratory decline.
• Nutritional deficiencies (especially fat-soluble vitamins).
• Potential for diabetes and liver disease.

Summary

Cystic fibrosis is a complex, multi-system genetic disorder with significant impacts on respiratory and digestive systems, among others. While there is no cure, management focuses on alleviating symptoms, preventing complications, and improving life quality.