PURPOSE: As a result of newborn screening programs, individuals have been identified as possibly having cystic fibrosis (CF) on the basis of two genetic mutations of the CFTR protein (located on two different chromosomes) but having a normal sweat chloride test. Retesting of these infants, who are assigned the diagnosis of CRMS, have been recommended at two and six months of age (J Peds 2009;155:S106-16). Because not all CFTR mutations are disease-causing, there continues to be uncertainty as to the natural history of these newborns.
METHODS: We have identified a family with delta I507 with poly T (TG)12-5T and (TG)10-7T mutations. The newborn had three normal sweat chloride determinations (24, 20, and 30 mMol/L at 2, 4, and 12 months of age). However, his two older siblings with the same mutations show positive values of 71 and 76 mMol/L at 42 and 63 months of age. We then looked at fourteen of our CRMS patients and examined their sweat chloride test results and ages.
RESULTS: It appeared that there is a direct correlation between age and sweat Cl in patients with CRMS. On the other hand, patients with two mutations which are clearly associated with CFTR dysfunction (i.e., CF) will have positive sweat chlorides, even at two to four months of age. There was no correlation with the volume of sweat and the value of chloride in CRMS.
CONCLUSIONS: In conclusion, close follow-up of CRMS patients identified by newborn screening with re-testing of their sweat chloride is recommended. Extrapolating the data on our CRMS patients, it would appear that continued sweat chloride testing, especially after 40 months of age, may be necessary. This was also indicated by our family described above.
CLINICAL IMPLICATIONS: Newborns with CRMS may develop to atypical CF phenotype if repeat sweat testing is performed after 40 months of age.
DISCLOSURE: The following authors have nothing to disclose: Terry Chin, Sophia Williams, Inderpal Randhawa, Eliezer Nussbaum
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