A defective chloride channel causes thick secretions in every exocrine organ
Expansion
Defect: the CFTR gene on chromosome 7 encodes a cyclic AMP-regulated chloride channel. Autosomal recessive; the commonest mutation is delta F508, a deletion of three bases removing a single phenylalanine.
Consequence: impaired chloride and therefore water secretion, so exocrine secretions are thick and dehydrated throughout the body.
| Organ | Consequence |
|---|---|
| Lung | Impaired mucociliary clearance, chronic infection with Pseudomonas and Staphylococcus, bronchiectasis |
| Pancreas | Exocrine insufficiency with steatorrhoea; later CF-related diabetes |
| Gut | Meconium ileus in the neonate, distal intestinal obstruction later |
| Liver | Biliary cirrhosis |
| Sweat glands | High sweat chloride, the basis of the diagnostic test |
| Reproductive | Absent vas deferens in males, causing infertility |
The sweat test is diagnostic because the defect works in the opposite direction there: the duct normally reabsorbs chloride, so a faulty channel leaves sweat salty.
Modulator drugs are now transforming treatment by targeting the protein itself: correctors improve trafficking of misfolded delta F508 protein, and potentiators improve channel opening.