Supplement
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

https://doi.org/10.1016/j.jpeds.2009.09.003Get rights and content

Through early detection, newborn screening (NBS)1 for cystic fibrosis (CF) offers the opportunity for early intervention and improved outcomes. NBS programs screen for hypertrypsinogenemia, and most also identify mutations in the CF transmembrane conductance regulator (CFTR) gene. Individuals identified by NBS are diagnosed with CF if they have an elevated sweat chloride level or if they have inherited 2 disease-causing mutations in the CFTR gene. Mutations in the CFTR gene can cause CF, but not all CFTR mutations are disease-causing. The term CFTR-related metabolic syndrome (CRMS) is proposed to describe infants identified by hypertrypsinogenemia on NBS who have sweat chloride values <60 mmol/L and up to 2 CFTR mutations, at least 1 of which is not clearly categorized as a “CF-causing mutation,” thus they do not meet CF Foundation guidelines for the diagnosis of CF. With what is now near-universal CF NBS in the United States, an increasing number of infants with CRMS are being identified. Given our inadequate knowledge of the natural history of CRMS, standards for diagnosis, monitoring, and treatment are absent. This document aims to help guide the monitoring and care of individuals with CRMS while our knowledge base on appropriate management evolves.

Section snippets

Methods

The Delphi method was used prospectively and formally to determine consensus or lack thereof with the proposed recommendations.5 The CF Foundation charged a small working group with creating a general framework for monitoring and management of CRMS. Proposed care statements were circulated to a larger panel of 18 experts, which included representatives from the infant care guidelines group2 and the CF Center Directors in Massachusetts, a state with 5 CF care centers and 9 years of experience

Conclusion

When CF NBS identifies an infant with CRMS, a complex and potentially difficult situation is created for the family, CF specialist, and PCP. Care should be given to first, do no harm by creating a vulnerable child in the parents' eyes because many of these individuals will live a long and healthy life with a low risk for development of signs or symptoms of CF. However, because some will become symptomatic and preventive care is preferable to symptomatic care, these individuals should not be

Author Disclosures

Drucy Borowitz, MD, has served as a consultant for Solvay Pharmaceuticals. Stephanie D. Davis, MD, has served as a consultant for Inspire Pharmaceuticals. Frank J. Accurso, MD, has received funding from Digestive Care, Inc., Axcan Pharma, and Yasoo Health, Inc. The following authors declare no financial arrangement or affiliation with a corporate organization or a manufacturer of a product discussed in this supplement: Phil M. Farrell, MD, PhD, Bruce C. Marshall, MD, Richard B. Parad, MD, MPH,

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