Sweat Chloride Concentrations in Infants Homozygous or Heterozygous for F₅₀₈ Cystic Fibrosis

¹ Department of Pediatrics, University of Wisconsin, Madison

Objective. To determine whether an adequate volume of sweat could be obtained routinely from infants younger than 6 weeks old and to evaluate sweat chloride levels in infants with known genotype statuses, including heterozygote carriers for cystic fibrosis (CF).

Methodology. Infants were evaluated using pilocarpine iontophoresis and measurement of sweat volume and chloride concentration. The majority of these infants were referred because of newborn screening test results positive for CF based on immunoreactive trypsinogen analysis. DNA analyses for the 3-base pair deletion at codon 508 of the CF transmembrane regulator gene (F₅₀₈ mutation) were performed whenever possible, and patients with CF were categorized by genotype.

Results. Sweat tests were performed successfully (50 mg of sweat) in 99.3% of the infants tested, and there was no difference in the proportion of unsuccessful tests in infants younger than or older than 6 weeks of age. The normal mean ± SD sweat chloride was 10.6 ± 5.2 mEq/L (95% confidence interval, 9.9-11.3). Patients with CF who are F₅₀₈ homozygotes or F₅₀₈ compound heterozygotes or who have two other non-F₅₀₈ mutant alleles were shown to have similar sweat chloride levels, with mean values of 99.9, 98.8, and 96.6 mEq/L, respectively. The group of infants who were found to be CF (F₅₀₈) heterozygote carriers, when compared with the healthy group, had mildly but significantly increased sweat chloride concentrations, with a mean ± SD of 14.9 ± 8.4 mEq/L (95% confidence interval, 13.4-16.4).

Conclusions. Quantitative pilocarpine iontophoresis can be used successfully in infants younger than 6 weeks of age who are undergoing routine diagnostic evaluations to follow up newborn screening test results that are positive for CF. The upper limit of normal sweat chloride in infants should be revised to 40 mEq/L (mean + 3 SD of the CF heterozygote carrier group). CF heterozygote carrier infants with one F₅₀₈ mutant allele show phenotypic manifestations of CF, including subclinical elevations of sweat chloride.

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