Cystic fibrosis: Clinical

Cystic fibrosis, or CF, is an autosomal recessive disorder in which there’s a mutated “cystic fibrosis transmembrane conductance regulator” or CFTR protein.

The mutated CFTR protein causes secretions to be abnormally thick and sticky - and they build up in the lungs, pancreas, and other organ systems.

The CFTR protein is a channel protein that pumps chloride ions into various secretions. Those chloride ions help draw water into the secretions, which helps to thin out the secretion.

The most common mutation that leads to cystic fibrosis is the “∆F508” mutation. This mutation causes the CFTR protein to not make it to the cell membrane.

Without CFTR protein on the epithelial surface, chloride ions aren’t pumped into the secretions, and that leaves the secretions thick and sticky.

In some countries, diagnosis of cystic fibrosis is done with newborn screening. Usually it’s done by detection of a pancreatic enzyme called immunoreactive trypsinogen or IRT, which is released into the fetal blood when there’s pancreatic damage from CF.

A confirmatory test is the quantitative pilocarpine iontophoresis, better known as the sweat test, which detects high levels of chloride in the sweat.

The reason for this is that in the lungs and pancreas a mutated CFTR means that chloride can’t go out, but in the sweat glands a mutated CFTR means that chloride can’t come in, or be reabsorbed.

So if chloride levels in the sweat are high, meaning over 60 mmol/L, CF diagnosis is very likely, while intermediate levels, from 30 to 59 mmol/L in infants below 6 months or 40 to 59 mmol/L in older infants, children, and adults, mean CF diagnosis is possible.

In both cases, DNA testing is done to detect the most common cystic fibrosis-related mutations.

If two or more of these mutations are detected, one in each chromosome then the diagnosis of CF is confirmed.

Having said that, even if only one DNA mutation or no mutation at all is detected, an individual may still have cystic fibrosis, due to some rare mutation that standard genetic testing cannot detect.