✅ Model Answer:
• Diagnosis: Cystic fibrosis with pancreatic insufficiency.
• Evidence: Low fecal elastase (<100 μg/g), steatorrhea (elevated fecal fat), fat-soluble vitamin deficiencies (D, E), recurrent respiratory infections, poor weight gain.
• Next step: Sweat chloride test (>60 mEq/L confirms CF). CFTR genetic testing. Start pancreatic enzyme replacement therapy (PERT) and fat-soluble vitamin supplementation (ADEK). Multidisciplinary CF care.

✅ Model Answer:
• Gene: CFTR (cystic fibrosis transmembrane conductance regulator) located on chromosome 7q31.2.
• Inheritance: Autosomal recessive (both parents are carriers).
• Most common mutation: ΔF508 (deletion of phenylalanine at position 508) – accounts for ~70% of alleles in Caucasians.
• Pathophysiology: CFTR mutation → defective chloride transport across epithelial cells → thick, viscous secretions in lungs, pancreas, GI tract, and sweat glands.
• Prevalence: 1 in 2,500-3,500 live births (most common in Caucasians).

✅ Model Answer:
• Pulmonary:
- Recurrent respiratory infections: Pneumonia, bronchitis, sinusitis.
- Chronic cough, wheezing, dyspnea.
- Bronchiectasis: Progressive lung damage.
- Nasal polyps, sinusitis.
- Pneumothorax, hemoptysis.
• Pancreatic:
- Pancreatic insufficiency: Steatorrhea, poor weight gain, fat-soluble vitamin deficiencies (ADEK).
- Recurrent pancreatitis.
- Diabetes mellitus (CFRD) – in later years.
• Gastrointestinal:
- Meconium ileus in neonates.
- Distal intestinal obstruction syndrome (DIOS).
- Rectal prolapse.
• Other:
- Salty-tasting skin.
- Male infertility (absent vas deferens).
- Delayed puberty, growth failure.

✅ Model Answer:
• Sweat chloride test: Gold standard – chloride >60 mEq/L confirms CF (normal <40, borderline 40-60).
• Genetic testing: CFTR mutation panel (detects most common mutations).
• Newborn screening: Immunoreactive trypsinogen (IRT) + CFTR mutation analysis.
• Pancreatic function tests:
- Fecal elastase-1: <100 μg/g indicates pancreatic insufficiency.
- 72-hour fecal fat: Steatorrhea (>7 g/day).
• Pulmonary function tests: For older children.
• Chest X-ray/CT: Bronchiectasis, hyperinflation.
• Other: Nasal potential difference, intestinal current measurement (research).

✅ Model Answer:
• Pancreatic enzyme replacement therapy (PERT):
- Dose: 1,000-2,500 lipase units/kg/meal (or 500-1,000 units/kg/snack).
- Adjusted: Based on stool fat, weight gain, and symptoms.
- Monitor: Avoid fibrosing colonopathy (with high doses).
• Fat-soluble vitamin supplementation:
- ADEK: Vitamin A, D, E, K (water-miscible forms recommended).
- Dose: Age-appropriate (e.g., 800-1,000 IU vitamin D daily).
• Nutritional support:
- High-calorie diet: 120-150% of daily requirements.
- MCT oil: Supplement for easy absorption.
- Enteral feeding: NG/GT for failure to thrive.
• Pulmonary management:
- Chest physiotherapy, airway clearance.
- Bronchodilators, inhaled mucolytics (dornase alfa, hypertonic saline).
- Antibiotics: For infections (prophylactic or as needed).
• CFTR modulators: Ivacaftor, lumacaftor/ivacaftor, elexacaftor/tezacaftor/ivacaftor (for specific mutations).
• Multidisciplinary CF team.

✅ Model Answer:
• Pulmonary:
- Bronchiectasis, pneumothorax, hemoptysis.
- Respiratory failure.
- Lung transplantation (end-stage).
• Pancreatic:
- Pancreatic insufficiency → malabsorption.
- Pancreatitis (acute or chronic).
- Cystic fibrosis-related diabetes (CFRD).
• Gastrointestinal:
- Distal intestinal obstruction syndrome (DIOS).
- Rectal prolapse.
- Biliary cirrhosis, portal hypertension.
• Other:
- Infertility (males: absent vas deferens).
- Growth failure, delayed puberty.
- Osteoporosis, bone fractures.
- Psychological impact.

✅ Model Answer:
• Prognosis:
- Improved significantly with early diagnosis and multidisciplinary care.
- Median survival: Now >40 years (in developed countries).
- Life expectancy: Continues to increase with CFTR modulators.
- Pulmonary function: Major determinant of survival.
- Growth and nutrition: Good with PERT and nutritional support.
• Long-term follow-up:
- Annual monitoring: Spirometry, sputum culture, nutritional status, diabetes screening.
- Bone density.
- Psychosocial support.
- Transition to adult care.
- Genetic counseling for family members.

✅ Model Answer:
• Fecal elastase-1: A pancreatic enzyme that is not degraded in the intestine; reflects pancreatic exocrine function.
• Normal: >200 μg/g.
• Mild to moderate insufficiency: 100-200 μg/g.
• Severe insufficiency: <100 μg/g (suggests pancreatic insufficiency).
• Advantages:
- Non-invasive.
- Not affected by exogenous pancreatic enzyme replacement.
- Sensitive and specific for pancreatic insufficiency.
• Limitations: Can be falsely low in watery stools (dilution effect).
• Clinical use: First-line test for pancreatic insufficiency in CF, Shwachman-Diamond, and chronic pancreatitis.