For the diagnosis of cystic fibrosis according to), at least one diagnostic clue must be present and CFTR dysfunction must be demonstrated:
Screening for cystic fibrosis in Germany is performed in three stages as a serial combination of two biochemical tests for immunoreactive trypsin (IRT) and pancreatitis-associated protein (PAP) and DNA mutation analysis. Beginning September 1, 2016, newborns will also be screened for cystic fibrosis as part of their initial screening. Screening procedure:
- First stage (IRT) and second stage (PAP) are performed by conventional laboratory testing methods.
- If the IRT test is positive (value ≥ the 99.0th percentile), a PAP test is performed from the available sample. If this is ≥ the 87.5th percentile, the third stage is performed.
- Third stage occurs if IRT as well as the also tested PAP in the blood are elevated (= suspected cystic fibrosis) → CFTR mutation analysis (Genetic Diagnostics Act!).
Cystic fibrosis screening is performed using the same blood sample as the extended newborn screening within the first four weeks of the child’s life.
Newborn screening (CF-NGS) in Switzerland consists of a two-step testing procedure:
- Heel blood test (= Guthrie test; 4th day of life) – immunoreactive trypsinogen (IRT) is measured.
- DNA screening for CF gene mutations
All children screened positive are referred to a CF center for diagnostic workup (sweat test and genetic diagnosis). The two-step procedure achieved a preliminary sensitivity (percentage of diseased patients in whom the disease is detected by the use of the test, i.e. a positive test result occurs) of 96.8% and specificity (probability that actually healthy people who do not have the disease in question are also detected as healthy in the test) of 99.9% (as of May 2013).
1st order laboratory parameters – obligatory laboratory tests (to detect CFTR dysfunction).
- Sweat test (using pilocarpine iontophoresis for clinical detection of cystic fibrosis (= pilocarpine iontophoresis sweat test); the test is routinely performed in newborn screening; gold standard) [increased chloride ion content is found in the sweat of cystic fibrosis patients compared with healthy subjects:
- “intermediate” chloride levels: 30-59 mmol/l → follow-up until 5 years of age due to possibility of “delayed” (“delayed”) CF; 86% of delayed CF diagnoses were made by the second year of life
- ≥ 60 mmol/l and/or a corresponding genetic defect (see below) = cystic fibrosis patient (CF patient)]
- Molecular genetic testing – CFTR genetic mutation analysis (mutations Delta F508/F508del (40-50% of cases), G542x, G551D, 621+1 (G>T), R553X, N1303K) in case of positive sweat test.
2nd order laboratory parameters (to detect CFTR dysfunction).
- Nasal potential difference (NPD) or intestinal short-circuit current (ICM) measurement – to detect a characteristic abnormality of CFTR function.
Cystic fibrosis can be excluded if [guidelines: S2k guideline]:
- No elevated sweat chloride levels in at least 2 independent measurements and.
- No causative mutations in a complete analysis of the CFTR gene and
- Inconspicuous findings in the NPD and/or ICM were detected.
