What Tests Are Available to Diagnose Cystic Fibrosis?

Patient Presentation
A 2-year-old caucasian male came to clinic with his mother for his health maintenance visit.
She had no concerns about him, but she was 8 weeks pregnant and had just learned that her sister’s new baby was diagnosed with cystic fibrosis (CF).
The mother said her niece was 2 months old, healthy, was diagnosed by a blood test and was going to see the specialists soon.
She said that the families were shocked because no one in her family nor the father’s family had CF.
She says that she has already made her first prenatal appointment but it is scheduled in 2 weeks and she has lots of questions about testing her unborn child.
The family history is negative for fetal, infant, or unexpected deaths. There were no gastrointestinal or pulmonary diseases. The father had seasonal allergic rhinitis.
The pertinent physical exam of the 2 year old male is unremarkable.
The diagnosis of a healthy 2 year old male is made. The physician told the mother that prenatal testing of the parents and the fetus were available, but
that without more information about the niece he could be more specific about the overall risk of CF for the fetus. The physician also recommended that the mother obtain as much specific information about the niece as possible as this would help increase the accuracy in determining the risk for the fetus.
The physician gave an information prescription to the mother with Internet resources about CF that she could consult.
She was also told to consider contacting her obstetrician for a possible earlier appointment.
The mother’s clinical course was that she had blood DNA testing for CF at her prenatal appointment and was found to be a carrier of the ΔF508 CF mutation. The father then was tested and found to be negative.
Therefore they were counseled that the fetus should not have CF and should either be normal or be a carrier. Carrier testing could be offered when the child was older.

Cystic fibrosis (CF) is a common autosomal recessive genetic disease. It occurs worldwide in all ethnic groups. In northern European ethnicity it has an incidence of 1:3200 live births. In African-Americans it is 1:15,000 births and occurs less commonly in Asian populations.
The carrier risk in Caucasians is ~4%.

The mutation is on the long arm of chromosome 7. The most common mutation is a 3 base pair deletion causing loss of a phenylalanine at the 508 position of the protein molecule. This ΔF508 causes 70-80% of the mutations, and at least 850 other mutations have been identified.

CF is a disease of ion channel regulation. There is an impermeability of chloride ions in epithelial cells, leading to dysregulation of ions (including sodium) and fluid. This simplistically leads to increased viscosity of secretions and blockage of ducts and airways.
The average life span is ~35 years currently.

Any organ with an epithelial surface can be affected, but major clinical manifestations include:

  • General – malnutrition, growth failure, delayed puberty
  • Pancreas – mainly exocrine dysfunction but also secondary endocrine dysfunction
  • Intestine – intestinal obstruction, meconium ileus
  • Liver – cholelithiasis, cholestasis and cirrhosis
  • Pulmonary – chronic bronchopulmonary infection especially with Pseudomonas aeruginosa, emphysema
  • Skin – high sweat electrolyte with depletion in a hot environment
  • Genitourinary – infertility

Learning Point
Tests that are currently available for CF include:

  • Sweat testing – a sweat chloride concentration >60 meq/L on at least 2 samples that are properly collected with an adequate amount of sweat (>100 mg) is diagnostic. Borderline tests (i.e. 40-60 meq/L) need to be re-tested. Because it is almost impossible to test for all the possible mutations, a person usually is not diagnosed with CF unless the sweat test is positive.
    The sweat test can be difficult to perform properly and therefore a patient may need to be sent to a CF center or other large institution that regularly performs the test.

  • DNA testing – is usually done for the ΔF508 mutation plus other common local mutations. It is becoming easier to test for more mutations. DNA testing can be done on blood, buccal brushings, chorionic villous or amniocentesis samples.
  • Immunoreactive trypsinogen – infants with CF have abnormally high levels of immunoreactive trypsinogen (IRT) in their serum and this is the basis for its use in newborn screening programs. The blood spots on Guthrie cards can be screened, and if abnormal, followup tests conducted.
    These tests include DNA analysis and/or repeated IRT testing depending on the local circumstances.

  • Nasal potential differences or nasal PD – can be performed at some CF centers by measuring the electric voltage difference across the nasal epithelium.

Questions for Further Discussion
1. What are the current treatments for CF?
2. Why is Pseudomonas aeruginosa more common in patients with CF?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Information prescriptions for patients can be found at MedlinePlus for these topics: Cystic Fibrosis and Newborn Screening
and at Pediatric Common Questions, Quick Answers for this topic: Birth Defects

To view current news articles on this topic check Google News.

Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:1967-1980.

Gross SD, Boyle CA, Botkin JR, Comeau AM, Kharrazi M, Rosenfeld M, Wilfond BS. Newborn Screening for Cystic Fibrosis. Evaluation of Benefits and Risks and Recommendations for State Newborn Screening Programs.
MMWR. 2004;53(RR13);1-36. Available from the Internet at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5313a1.htm (cited 9/11/06).

J Massie, L Curnow, N Tzanakos, I Francis, C F Robertson. Markedly elevated neonatal immunoreactive trypsinogen levels in the absence of cystic fibrosis gene mutations is not an indication for further testing.
Arch. Dis. Child. 2006;91:222-225. Available from the Internet at: http://adc.bmjjournals.com/cgi/content/abstract/91/3/222?lookupType=volpage&vol=91&fp=222&view=short (cited 9/11/06).

Price JF. Newborn screening for cystic fibrosis: do we need a second IRT? Arch Dis Child. 2006;91(3):209-10. Available from the Internet at: http://adc.bmjjournals.com/cgi/content/full/91/3/209 (cited 9/11/06).

Online Mendelian Inheritance in Man. Cystic Fibrosis. National Institutes of Health and Johns Hopkins University. Available from the Internet at: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=219700 (rev. cited 9/14/06).

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    6. Information technology to support patient care decisions and patient education is used.
    7. All medical and invasive procedures considered essential for the area of practice are competency performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    12. Evidence from scientific studies related to the patients’ health problems is located, appraised and assimilated.
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.
    15. Information technology to manage information, access on-line medical information and support the healthcare professional’s own education is used.

  • Interpersonal and Communication Skills

    18. Using effective nonverbal, explanatory, questioning, and writing skills, the healthcare professional uses effective listening skills and elicits and provides information.
    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Systems Based Practice
    23. Differing types of medical practice and delivery systems including methods of controlling health care costs and allocating resources are known.
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.
    25. Quality patient care and assisting patients in dealing with system complexities is advocated.
    26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.

    Donna M. D’Alessandro, MD
    Associate Professor of Pediatrics, Children’s Hospital of Iowa

    October 9, 2006