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CF gene mutation
The most common CFTR mutation is F508del, which accounts for about 70 percent of the mutations in those of Northern European descent. Testing of F508del in isolation or a panel of 50 common mutations of the CF gene has been developed to screen general or targeted populations for CF and CF carrier status. (The number of mutations screened within the panel varies between laboratories). These panels check the patient’s for each of the selected CF mutations. If two CF mutations are identified, the patient has CF. If one is located, the pperson is either a carrier or has CF with the second mutation unidentified. Further clinical assessment, genetic testing (sequencing of the CF gene) and a sweat test can be performed. A person of Northern European descent who tests negative for the F508del mutation has about a 1 in 100 chance of being a CF carrier. Someone of Northern European descent who tests negative for a panel of ~50 mutations has about a 1 in 130 chance of being a CF carrier.
This test involves measuring sodium and chloride from a sweat sample collected in a procedure in which local sweating is stimulated by using the drug, pilocarpine. The collected sweat is weighed on filter paper and the concentrations of sodium and chloride measured. Since the CFTR protein is altered or missing and chloride travel is restricted, the sweat in somone with CF may be up to five times saltier than normal. Positive results are confirmed and followed with CF gene mutation testing. Some people with CF can be diagnosed using only sweat testing. Rarely, people with definite CF, often with unusual mutations, have sweat sodium and chloride levels within the normal range.
Faecal chymotrypsin is a stool test for proteolytic enzymes. These enzymes are produced in an inactive form in the pancreas and then activated in the small intestine to digest food proteins. Low values indicate pancreatic insufficiency in people with CF who have not been treated. In those people being treated with pancreatic enzyme replacement therapy, values are usually normal. However, they do not correlate closely with the amount of fat in the stools.
Faecal pancreatic elastase 1
This is now the best indirect measure of pancreatic function and it has superseded a number of indirect pancreatic function tests including the bentiromide and pancreolauryl tests. Faecal pancreatic elastase 1 is a protease (an enzyme that breaks down proteins) produced by the pancreas. It is found in the faeces. Measured in a stool sample it provides an accurate assessment of pancreatic function. In someone with CF, levels are significantly lower than normal. Levels are not affected by exocrine pancreatic treatment.
Immunoreactive trypsin (IRT)
This newborn screening test for CF is performed on the blood spots collected on Guthrie screening cards. In CF, thick mucus plugs can obstruct pancreatic ducts and prevent a digestive enzyme, trypsinogen from reaching the intestine. Blood IRT levels will be elevated in most newborns who have CF. The IRT test has 95 to 98 per cent (some affected babies and those with mild disease may be missed). Elevated IRT in the first few days of life can also be caused by perinatal stress, renal failure, congenital infection, bowel atresia and some aneuploidies. An elevated IRT is usually followed with DNA testing for four most often seen CFTR mutations including the F508del mutation for neonatal CF screening. Early diagnosis is essential so that treatment can be started before damage to the lungs with chronic infection occurs and malnutrition becomes established.
Other laboratory tests used to check lung infection, organ function and fertility include:
Non-laboratory tests that may be performed include respiratory function tests, chest X-rays, lung scans including low-dose CT scan to look for air trapping and early bronchiectasis, bronchoscopies, bone scans, upper GI and small bowel X-rays and other gastrointestinal pancreatic and liver investigations such as ultrasound scans.
Last Review Date: July 29, 2016