Cystic Fibrosis

Other Names

CF

Cystic fibrosis of the pancreas

Mucoviscidosis

Diagnosis Coding

E84.9, cystic fibrosis, unspecified

Disorder Category

An exocrine disorder

Screening

Finding

All 50 states screen newborns for cystic fibrosis (CF), though the method of testing varies. Trypsinogen, which is produced only in the pancreas, is elevated in infants with CF and is tested for by an immunoassay (immunoreactive trypsinogen or IRT). State programs react to a high IRT screening level in several ways: some go directly to genetic testing, some repeat the IRT and, if both tests are abnormal, notify the primary care physician (PCP), some repeat the IRT and then send the blood spot for genetic testing and, if genetic testing shows one of the CFTR mutations, then notify the PCP and family. All positive testing on the newborn screen, whatever the method, should be followed by sweat chloride testing, the gold standard for diagnosis. Infants born, or presenting in the first few days of life, with meconium ileus due to CF may have normal trypsinogen levels and would therefore not test positive on newborn screening. Infants with meconium ileus are tested directly with DNA and sweat chloride testing.

Tested By

Immunoassay for trypsinogen (immunoreactive trypsinogen test, or IRT); followed by repeat testing and/or CFTR mutation analysis, depending on the state.

Overview

CF occurs when a patient carries two deleterious mutations for cystic fibrosis transmembrane conductance regulator (CFTR) function (see CFTR Gene (Genetics Home Reference)). CFTR mutations result in impaired chloride ion channel function and abnormal secretions in sweat glands, lungs, liver, pancreas, digestive system, sinuses, and reproductive system. This accumulation of thick and sticky secretions results in decreased organ function, especially in the lungs, and makes patients prone to pulmonary infections. In addition, individuals with CF may have difficuly absorbing nutrients, causing malnutrition and fatty stools. With recent advancements in care, individuals with CF are living longer – current life expectancy is greater than 37 years.

Prevalence

Prevalence is 1:3,500 in white infants; 1:15,000 black infants; 1:7,000 Hispanic infants. It is less common in Asians. [Kaye: 2006]

Inheritance

Autosomal recessive; CF is caused by one of 1547 possible mutations of the CFTR gene on chromosome 7. Clinical & Functional Translation of CFTR for Clinicians (CF Foundation) The delta F508 mutation (the most common CF-related mutation) is found in 70-90% of children with CF. CFTR: The Gene Associated with Cystic Fibrosis (NHGRI) Although this mutation is generally associated with severe disease, [Dawson: 2001] [Mickle: 2000] the severity of disease is difficult to predict because it depends on several factors: which two mutations are present, modifier genes, epigenetic factors, and the environment. [Gallati: 2003] Rarely, individuals with CFTR gene mutations may be asymptomatic.

Maternal & Family History

Maternal carrier genetic testing is offered to women of child-bearing age. Carrier Screening for Cystic Fibrosis (ACOG) Parents may opt out of this testing. Not all insurance carriers cover carrier testing.

Prenatal Testing

DNA testing of samples obtained by amniocentesis or chorionic villus sampling (CVS) is available; most screens look for 30+ mutations, although over 1500 known mutations are known to cause CF (see Clinical & Functional Translation of CFTR for Clinicians (CF Foundation). If there is a family history of CF, prenatal testing should include known family mutations.

Other Testing

Sweat testing is performed when there is meconium ileus or a positive newborn screen. Because newborn screening genetic testing looks for only a small number of disease-causing mutations, sweat chloride testing should be performed if a child is symptomatic, regardless of the screening results. Additional and more detailed genetic testing may be needed for positive or borderline sweat test results. The CF Foundation certifies only a limited number of sweat chloride testing sites – see CF Newborn Screening – Info for Parents (CF Foundation). Other institutions may utilize sweat conductivity which is a screening test, not a diagnostic test.

Clinical Characteristics

With treatment, health complications are reduced and survival into middle adulthood is common. The CF Foundation has established care centers, certified sweat chloride testing, advocated for CF newborn screening, and more, all of which have helped survival in children with CF. [Schechter: 2010] Without treatment, symptoms may vary. With more severe CFTR mutations, acute and chronic respiratory infections, chronic digestive complications, diabetes, and other symptoms can be expected. Children with two severe mutations generally have malabsorption in the newborn to early childhood period. One mild mutation in conjunction with a severe mutation often results in pancreatic sufficiency. These patients may not need pancreatic enzyme supplementation. The presentation of CF-related lung disease cannot always be predicted by the severity of the CFTR mutation.

Initial symptoms may include:
  • Meconium ileus
  • Salty sweat or sweat crystals on the skin
  • Poor weight gain
  • Smelly, greasy, bulky, and bright green stools (even in breast fed infants)
  • Diarrhea, constipation, or persistent abdominal pain
  • Rectal prolapse
  • Persistent coughing or wheezing
  • Thick phlegm and mucus
  • Recurrent lung and sinus infections
  • Nasal polyps

If not treated, patients may experience:
  • Malnutrition and poor growth
  • Electrolyte depletion
  • Pulmonary damage or bronchiectasis
  • Diabetes
  • Pancreatitis
  • Liver disease
  • Death in childhood

Follow-up Testing after Positive Screen

States use different screening algorithms for testing. For example, infants born in Utah are considered to have a positive screening test if two IRT specimens are elevated and if genetic testing for CFTR mutations is positive. In Idaho, infants are considered to have a positive screen if two IRT specimens are elevated and the Medical Home is then responsible to assure the patient receives sweat chloride diagnostic testing, gene analysis, and treatment. In most centers, genetic counseling is scheduled during the sweat chloride test. [Farrell: 2008]

Sweat chloride testing is the gold standard for identifying children with CF. Stimulated by pilocarpine iontophoresis, sweat is collected on gauze and the amount of sweat and chloride is determined. Standard values vary by age group. Children with CF demonstrate high chloride levels in sweat because uptake of chloride into the sweat duct is impaired. If the test is equivocal, further testing is indicated and the child should be evaluated by a cystic fibrosis center. If the test is positive, the infant will receive an appointment in 72 hours (unless extenuating circumstances arise), with treatment started at that time.

Though uncommon, DNA testing may be falsely negative. If symptoms consistent with CF are present, despite a normal newborn screen result, sweat chloride testing should always be performed.

Primary Care Management

Upon Notification of the + Screen

  • Contact the family and work with the see all Newborn Screening Programs services providers (3) in our database to set up sweat chloride testing to confirm/exclude the diagnosis and genetic testing as indicated. Sweat testing should be performed by an experienced laboratory, such as those associated with CF Foundation-Accredited Care Centers (CF Foundation).
  • If the sweat chloride testing is positive, follow-up will be initiated ASAP. Many patients will already have poor weight gain at the time a diagnosis is confirmed. Initiation of pancreatic enzyme supplementation as early as possible is vital to correcting nutritional deficiencies and preventing morbidity and mortality.
  • For ongoing collaborative management or consultation with the CF Foundation-Accredited Care Centers (CF Foundation).

If the Diagnosis is Confirmed

  • Ongoing education of the family regarding:
    • Signs, symptoms, and the need for urgent care when the infant becomes ill
    • Harmful effects of secondhand smoke
    • Hand washing to prevent infections
    • Need for a high salt, high fat, high protein diet (aiming for 150-180% of RDA), and extra fluids
    • Importance of Cystic Fibrosis Center management and follow up
  • Assure completion of routine immunizations, to include the 23-valent pneumococcal vaccine and annual influenza vaccines
  • Pancreatic enzymes and vitamin supplements may be indicated
  • Bronchodilators, mucus thinners, antibiotics, and other medications may be indicated

Specialty Care Collaboration

Initial consultation with a Cystic Fibrosis Center and specialists (usually pediatric pulmonologists and gastroenterologists) during the newborn period and ongoing collaboration with such a Center is critical to optimize outcomes. A dietician will work with the family to devise an optimal approach to dietary management. Genetic counselors will work with the family at the time of sweat testing. For evaluation and ongoing collaborative management, consult the following service(s): CF Foundation-Accredited Care Centers (CF Foundation).

Resources

Information & Support

For Professionals

ACT Sheet for Cystic Fibrosis (ACMG) (PDF Document 59 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Newborn Screening ACT Sheets & Confirmatory Algorithms (ACMG)
ACTion (ACT) Sheets and algorithms for responding to positive newborn screening test results, membership required; American College of Medical Genetics.

Cystic Fibrosis (OMIM)
Extensive review of literature that provides technical information on genetic disorders; Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University.

CFTR-Related Disorders (GeneReviews)
An expert-authored, peer-reviewed, current disease description that applies genetic testing to diagnosis and management information for disorders related to the CFTR gene.; National Center for Biotechnology Information, U.S. National Library of Medicine.

Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. Includes health supervision guidelines and other useful resources; a collaboration among the Health Resources & Services Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.

For Parents and Patients

Support

CF Foundation Utah/Idaho
A parent driven and administered educational, support, and advocacy site for families of children with cystic fibrosis followed at the Intermountain CF Center.

Cystic Fibrosis Foundation
A nonprofit organization that offers extensive information about CF, including frequently asked questions; testing and treatments; research; scholarships for individuals with CF; understanding insurance options; and, a link to Cystic Fibrosis Services, which provides pharmacy services; links to local chapters; support services; and more.

General

Cystic Fibrosis (MedlinePlus)
An overview of the condition with links to other organizations providing more information; from the National Library of Medicine.

Cystic Fibrosis (Genetics Home Reference)
Detailed review aimed at patients and families from the National Library of Medicine's Genetics Home Reference site.

Cystic Fibrosis Information (UDOH) (PDF Document 731 KB)
Information regarding testing for and early complications of CF; Newborn Screening Program, Utah Department of Health.

What Is Cystic Fibrosis? (NHLBI, NIH)
Information about cause, prevalence, signs and symptoms, diagnostic tests, treatments, and links to other organizations; National Heart Lung and Blood Institute and National Institutes of Health.

Cystic Fibrosis: Diet and Nutrition (KidsHealth.org)
Information for kids from a national site, sponsored by Nemours Foundation. Also provides pages for parents and teens (see tabs at the top of the page).

Practice Guidelines

Borowitz D, Parad RB, Sharp JK, Sabadosa KA, Robinson KA, Rock MJ, Farrell PM, Sontag MK, Rosenfeld M, Davis SD, Marshall BC, Accurso FJ.
Cystic Fibrosis Foundation practice guidelines for the management of infants with cystic fibrosis transmembrane conductance regulator-related metabolic syndrome during the first two years of life and beyond.
J Pediatr. 2009;155(6 Suppl):S106-16. PubMed abstract

Borowitz D, Robinson KA, Rosenfeld M, Davis SD, Sabadosa KA, Spear SL, Michel SH, Parad RB, White TB, Farrell PM, Marshall BC, Accurso FJ.
Cystic Fibrosis Foundation evidence-based guidelines for management of infants with cystic fibrosis.
J Pediatr. 2009;155(6 Suppl):S73-93. PubMed abstract

Patient Education

CF Fact Sheets (CF Foundation & Children's Hospital Boston)
Factsheets covering nutrition, tests, medications, schools, and more.

Services

Newborn Screening Programs

See all Newborn Screening Programs services providers (3) in our database.

Sweat Testing

See all Sweat Testing services providers (1) in our database.

For other services related to this condition, browse our Services categories or search our database.

Helpful Articles

PubMed search for cystic fibrosis in children, last 1 year

Grosse 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 Recomm Rep. 2004;53(RR-13):1-36. PubMed abstract / Full Text

Castellani C, Southern KW, Brownlee K, Dankert Roelse J, Duff A, Farrell M, Mehta A, Munck A, Pollitt R, Sermet-Gaudelus I, Wilcken B, Ballmann M, Corbetta C, de Monestrol I, Farrell P, Feilcke M, Férec C, Gartner S, Gaskin K, Hammermann J, Kashirskaya N, Loeber G, Macek M Jr, Mehta G, Reiman A, Rizzotti P, Sammon A, Sands D, Smyth A, Sommerburg O, Torresani T, Travert G, Vernooij A, Elborn S.
European best practice guidelines for cystic fibrosis neonatal screening.
J Cyst Fibros. 2009. PubMed abstract

Authors

Author: Barbara Chatfield, MD - 6/2010
Content Last Updated: 7/2010

Page Bibliography

Dawson KP, Frossard PM, Al-Awar B.
Disease severity associated with cystic fibrosis mutations deltaF508 and S549R(T-->G).
East Mediterr Health J. 2001;7(6):975-80. PubMed abstract

Farrell PM, Rosenstein BJ, White TB, Accurso FJ, Castellani C, Cutting GR, Durie PR, Legrys VA, Massie J, Parad RB, Rock MJ, Campbell PW 3rd.
Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report.
J Pediatr. 2008;153(2):S4-S14. PubMed abstract / Full Text

Gallati S.
Genetics of cystic fibrosis.
Semin Respir Crit Care Med. 2003;24(6):629-38. PubMed abstract

Kaye CI, Accurso F, La Franchi S, Lane PA, Hope N, Sonya P, G Bradley S, Michele A LP.
Newborn screening fact sheets.
Pediatrics. 2006;118(3):e934-63. PubMed abstract / Full Text

Mickle JE, Cutting GR.
Genotype-phenotype relationships in cystic fibrosis.
Med Clin North Am. 2000;84(3):597-607. PubMed abstract

Schechter MS, Gutierrez HH.
Improving the quality of care for patients with cystic fibrosis.
Curr Opin Pediatr. 2010;22(3):296-301. PubMed abstract