CF Mutation Panel. The American College of Medical Genetics (ACMG) and the American College of Obstetricians and Gynecologists (ACOG) recommend that a panel of 23 of the most common CFTR mutations be used to screen general or targeted populations for cystic fibrosis and CF carrier status. Some laboratories use expanded panels of up to 100 or more mutations designed to pick up rare mutations particular to specific ethnic populations. These may provide slightly better sensitivity to detect mutations in some specific ethnic populations but are not recommended by ACOG for general screening. Some rare mutations are seen in only a few individuals and may not be detected with routine testing, even with an expanded panel. Screening panels check the patient's DNA for each of the selected CF-causing mutations. ACOG recommends that CF screening be offered to all women of reproductive age. Prenatal and preconception carrier screening for CF is generally offered to the biological mother first. If the mother is a CF carrier, then the biological father should be tested. ACMG recommends that a positive result for the mother should include the recommendation of testing her partner and at-risk family members and that all positive results for diagnostic tests or for positive/positive couple screening should indicate the need for genetic counseling. In addition, all CFTR carriers and any individuals who have a family history of CF should also be referred for genetic counseling.
Sweat Test. This test involves measuring chloride from a sweat sample collected through a special procedure. Since the CFTR protein is altered or missing and chloride travel is restricted, the sweat of a person with CF may be up to five times saltier than normal. Positive sweat chloride test results should be confirmed and followed with CF gene mutation testing whenever possible.
Trypsin/Chymotrypsin. This is a stool test for proteolytic enzymes, which are produced in an inactive form in the pancreas and then activated in the small intestine to digest dietary proteins. Trypsin and chymotrypsin are detectable in both the small intestine and in the stool if the pancreas is functioning normally. A positive result, indicating the presence of trypsin and chymotrypsin in the stool, is normal. A negative result is not diagnostic, but it does indicate that further testing for CF may be indicated.
Immunoreactive Trypsinogen (IRT). This test is a newborn screening tool for trypsinogen, which is produced in the pancreas and transported to the intestine, where it is activated to form the enzyme trypsin. In CF, thick mucus can obstruct pancreatic ducts and prevent trypsinogen from reaching the intestine. Blood IRT levels will be elevated in newborns with CF, but positive results must be followed by confirmatory testing.
Nasal (transepithelial) Potential Difference (NPD). The active transport of ions, primarily sodium and chloride, across the respiratory epithelium, a layer of cells that line the nasal cavity, generates a potential difference (PD) that can be measured. The abnormal sodium and chloride transport in the respiratory epithelia of people with CF is associated with a different pattern of nasal PD compared to normal epithelia. The NPD technique examines particular features of this NPD to help establish a diagnosis of CF.
Other tests used to check organ function, fertility, and to detect lung infections include:
- Fecal fat
- Comprehensive metabolic panel (CMP)
- Basic metabolic panel (BMP)
- Complete blood count (CBC)
- Liver function tests
- Semen analysis
- Sputum cultures
Non-laboratory tests that may be done include bone and chest X-rays, upper GI and small bowel series, and lung function tests.