Supplement
Guidelines for Diagnosis of Cystic Fibrosis in Newborns through Older Adults: Cystic Fibrosis Foundation Consensus Report

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Newborn screening (NBS) for cystic fibrosis (CF) is increasingly being implemented and is soon likely to be in use throughout the United States, because early detection permits access to specialized medical care and improves outcomes. The diagnosis of CF is not always straightforward, however. The sweat chloride test remains the gold standard for CF diagnosis but does not always give a clear answer. Genotype analysis also does not always provide clarity; more than 1500 mutations have been identified in the CF transmembrane conductance regulator (CFTR) gene, not all of which result in CF. Harmful mutations in the gene can present as a spectrum of pathology ranging from sinusitis in adulthood to severe lung, pancreatic, or liver disease in infancy. Thus, CF identified postnatally must remain a clinical diagnosis. To provide guidance for the diagnosis of both infants with positive NBS results and older patients presenting with an indistinct clinical picture, the Cystic Fibrosis Foundation convened a meeting of experts in the field of CF diagnosis. Their recommendations, presented herein, involve a combination of clinical presentation, laboratory testing, and genetics to confirm a diagnosis of CF.

Section snippets

Sweat Chloride Test

The measurement of sweat electrolyte concentrations has been the mainstay of diagnosing CF since a standardized procedure, known as the Gibson-Cooke method, was established in 1959.24 Subsequent analysis of isolated single sweat ducts identified chloride as the principle electrolyte affected in CF.25 The discovery of CFTR confirmed the role of electrolyte transport in the etiology of CF and gave a molecular rationale to the sweat test for diagnosing CF. Although the ability to test for CFTR

Conclusion

The diagnostic procedures recommended herein recognize the wide possible range of disease severity and permit some leeway in the diagnosis of an individual while still creating a threshold for a diagnosis of CF. As was the case in 1996, the recommendations are based on the current state of the knowledge and should be considered a “work in progress,” leaving room for improvement resulting from increased insight into CF manifestations, genetics, and pathobiology. Nevertheless, it is hoped that

Author Disclosures

Philip M. Farrell, MD, PhD serves the Cystic Fibrosis Foundation as national facilitator for implementation of newborn screening and receives compensation for his efforts. Terry B. White, PhD who compiled the first draft of the manuscript, is an employee of the Cystic Fibrosis Foundation. Garry R. Cutting, MD holds patents on 2 of the CFTR mutations in the ACMG Panel suggested in this article for use in DNA analysis (Table II), as well as patents on CFTR mutations not included in the ACMG

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    Supported by funds from the Cystic Fibrosis Foundation.

    Please see the Author Disclosure section at the end of this article.

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