Diagnosis

Early screening

Prenatal Screening

Because CF is a genetic disease, it is possible to perform genetic testing on parents to see if they are carriers of CF genes. The test is conducted by comparing a DNA sample from both parents against a panel of known CF mutations.

There are different approaches to the screening process. For example, it may be a sequential testing where only one person of the couple is tested, and only if that person tests positive is the other person tested. Since CF is an autosomal-recessive disease, both parents must be carriers. If both parents are found to be carriers of CF mutations, other tests, such as chorionic villus sampling (CVS) or an amniocentesis, may be performed.

DNA tests for CF are expensive and, because of the broad variety of possible mutations, do not necessarily prove conclusively that a fetus will have CF. Consequently, prenatal screening is usually conducted on persons who are at sufficiently high risk to justify testing. They are usually couples who have a family history of CF.

Neonatal Screening

Another method for early identification and diagnosis of CF is done after birth as neonatal screening or newborn screening (NBS).

Both the Centers for Disease Control and Prevention (CDC), and the Cystic Fibrosis Foundation recommend NBS. Currently, 36 states mandate NBS for CF, although in 5 states it is not yet implemented.^24,25

NBS techniques rely on identification of immunoreactive trypsinogen (IRT). IRT is a pancreatic marker usually elevated in the blood of infants with CF.

Although the test is not 100% reliable, data from states that have been conducting NBS show convincing benefits in the area of nutrition and growth. Failure to thrive is associated with increased risk of childhood morbidity and death. ²⁵The test is typically done with a small blood sample, usually drawn using a heel-prick technique, on which a panel of various screens may be conducted.

Either a negative result in a patient with other symptoms or a positive result requires a repeat IRT and/or additional testing. Positive IRT results require DNA analysis and/or the sweat test²⁴. Although it may be difficult to collect sweat in some infants, the sweat test can be performed as early as 48 hours after birth, and more reliably at 4 weeks after birth.²⁶

Differential Diagnosis

When there has not been any DNA screening conducted, a CF diagnosis must await the presentation of symptoms and a differential diagnosis.

Differential diagnosis simply means ruling out other causes for the symptoms and narrowing down the field of possibilities. Symptoms of CF can mimic other illnesses, and in some patients only one organ is affected. In these cases, the physician tries to rule out other possibilities first.

More often, patients show multiple signs of CF, prompting the clinician to perform appropriate tests to confirm the diagnosis. These tests will be reviewed in greater detail later in this module. In the United States in 1996, the mean age at diagnosis of CF was 4.8 years.⁹

References:
9. Farrell PM, Kosorok MR, Rock MJ, et al. Early diagnosis of cystic fibrosis through neonatal screening prevents severe malnutrition and improves long-term growth. PEDIATRICS 2001;107:1-13.
24. Comeau AM, Accurso FJ, White TB, et al. Guidelines for implementation of cystic fibrosis newborn screening programs: cystic fibrosis foundation workshop report. Pediatrics 2007;119:495-518.
25. Denise R. Green, Scott D. Grosse, Marie Earley, and Joanne Mei Newborn Screening for Cystic Fibrosis: A Public Health Responsedation: CDC Genomics and Population Health 2005. Available at: http://www.cdc.gov. Accessed - 11/02/2009.
26. LeGrys VA. Assessment of sweat-testing practices for the diagnosis of cystic fibrosis. Arch Pathol Lab Med 2001 November;125:1420-4.