Cystic Fibrosis (pathology)

Question 1

What kind of mutation is cystic fibrosis

Answer 1

Autosomal recessive

Question 2

What is cystic fibrosis?

Answer 2

Mutation in transmembrane conductance regulator protein (CFTR) on Chr 7
- normal protein= chloride moves out of cell – no mucus build up
- abnormal protein= chloride stuck in the cell- Na+ and H2O stay with chloride- mucus build up outside of cell-> mucus collects bacteria
↓ mucociliary clearance
- Mucus sticks to mucosa-> inflammation + ↑ bacterial access = ↓ bacterial killing

Question 3

What are the 6 classes of mutation in CFTR?

Answer 3

1-3 severe disease

• Pancreatic insufficient
• -> 𝚫F508 class 2= severe disease
• 4-5 milder disease
• Some pancreatic function

Question 4

What is pancreatic insufficiency?

Answer 4

• Lack of pancreatic enzymes (trypsin, colistin)
• Fat Malabsorption
• Abnormal stool-steatorrhea
• Failure to thrive

Question 5

What are common co-morbidities of CFTR

Answer 5

Pancreatic insufficiency 
Repeated lung infection
Progressive bronchiectasis 
Scarring
Abscesses
Type 2 diabetes 
Osteoporosis

Question 6

Investigations for CFTR

Answer 6

Antenatal testing (if affected parent/sibling):
- Pre-implantation genetic diagnosis
- Chorionic villus sampling
- Amniocentesis
Neonatal screening:
- New-born bloodspot day 5 (Guthrie test)
- +ve-> clinical assessment & sweat test
- Sweat test- measure chloride concentration in sweat
- >60 mmol/l= abnormal

Question 7

Diagnostic outcome of CFTR investigations

Answer 7

1. CF
2. not CF
3. CF - screen positive inconclusive diagnosis (SPID)

Question 8

Management of CFTR

Answer 8

Management involves treating the many other co-morbidities associated with CFTR & modulator drugs
- KAFTRIO (small benefit in lung function)

Co-morbidities E.g.

- mucus obstruction (physiotherapy, mucolytics, bronchodilators)
- lung infection (antibiotics)