Makindo Medical Notes

Related Subjects: |Cystic Fibrosis |Sweat Test |Osteoporosis |Malabsorption |Bronchiectasis |Pseudomonas infection (Pseudomonas aeruginosa) |Autosomal Recessive |Genetic Mutations |Clustered Regularly Interspaced Short Palindromic Repeats CRISPR

⚠️ Cystic Fibrosis (CF) can present unexpectedly and severity varies widely. ✅ Elevated chloride in a pilocarpine-induced sweat test is diagnostic. 🦠 Interestingly, carriers have partial resistance to cholera as the toxin cannot open the chloride channels in the small intestine. 💡 With modern care, the UK median survival now exceeds 50 years.

📖 About

• Inherited defect of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein.
• Results in production of thick, viscid mucus → obstruction and recurrent infection.
• Multisystem disorder: respiratory, gastrointestinal, endocrine, reproductive, musculoskeletal.

🧬 Aetiology

• Autosomal recessive inheritance;>800 mutations identified.
• CFTR gene on chromosome 7q31.2.
• Over 70% cases due to ΔF508 mutation (misfolded CFTR protein).
• Genotype is a poor predictor of severity due to modifier genes and environment.
• Incidence: ~1 in 2,500 live births in the UK; carrier frequency ~1 in 25.

🧪 Gene Mutations & Effects

🔍 Diagnosis

• Detected on newborn screening (elevated immunoreactive trypsinogen → sweat/gene test confirmation).
• Clinical manifestations + positive sweat chloride test (≥60 mmol/L).
• Genetic confirmation (two pathogenic CFTR mutations).
• Rarely, diagnosis made on clinical grounds if tests inconclusive but features typical.

🧪 Investigations

• Sweat chloride test: Gold standard; ≥60 mmol/L diagnostic; 30–59 borderline.
• Genetic testing: Mutation analysis; informs prognosis and CFTR modulator eligibility.
• Pancreatic function: Faecal elastase (low = insufficiency).
• Respiratory evaluation: Baseline spirometry, chest X-ray/CT for bronchiectasis.
• Microbiology: Sputum cultures for Pseudomonas, Staphylococcus aureus, Haemophilus influenzae.
• Endocrine: OGTT or HbA1c (screen for CF-related diabetes).
• Fertility workup: Scrotal USS may show absent vas deferens; semen analysis in adults.

🫁 Clinical (Pulmonary)

• Chronic cough, recurrent chest infections, bronchiectasis.
• Pseudomonas colonisation → progressive decline.
• Complications: pneumothorax, massive haemoptysis, chronic rhinosinusitis, nasal polyps.

🍽️ Clinical (Gastrointestinal)

• Meconium ileus in neonates (10–20%).
• Pancreatic insufficiency → malabsorption, steatorrhoea, failure to thrive.
• Distal intestinal obstruction syndrome (DIOS).
• Fatty liver, biliary cirrhosis, gallstones.
• Secondary diabetes in up to 50% of adults.

🧍 Other Systems

• Finger clubbing, osteoporosis, CF-related arthritis.
• Male infertility (congenital bilateral absence of vas deferens).
• Female subfertility due to thick cervical mucus.
• Salty-tasting sweat (often first noticed by parents).

📊 Summary of Testing

⚠️ Complications

• Chronic respiratory failure, pulmonary hypertension, cor pulmonale.
• Recurrent chest infections and bronchiectasis.
• CFRD (cystic fibrosis–related diabetes).
• Osteoporosis, delayed puberty, renal calculi.
• Chronic liver disease, gallstones.
• Reduced fertility/infertility.

💊 Management

📚 References

• NICE guidance on CF (NG78)
• Ong T, et al. Cystic fibrosis in adults: management of respiratory disease. BMJ 2021.
• Cystic Fibrosis Trust UK resources.