Genotype analysis and phenotypic manifestations of children with intermediate sweat chloride test results

Study objectives: Cystic fibrosis (CF) is one of the most common inherited diseases among whites. Since the cloning of the CF transmembrane conductanc e regulator (CFTR) gene, a number of studies have focused on associations b etween the genotype and phenotype in CF, This had led to the progressive id entification of new groups of patients, including those who have mild lung disease and those who have normal sweat chloride values (< 60 mEq/L). The a im of the present work was to provide information on the genotype and the p henotypic characteristics of children with intermediate-range sweat chlorid e test results. Patients and results: We focused on children referred to the pulmonary depa rtment for various types of pulmonary disease and who had several sweat chl oride test results with median values in the range of 40 to 60 mEq/L. Twent y-four patients over a 10-year period were enrolled (mean age, 4.8 years). Respiratory manifestations at initial evaluation included recurrent bronchi -tis, wheezing, chronic cough, and pneumonia. The duration of the follow-up ranged from 0.5 to 10.5 years. Sputum cultures revealed the presence of Ha emophilus influenzae (10 children), Staphylococcus aureus (4 children), and Pseudomonas aeruginosa (3 children). Pancreatic insufficiency was found in two patients. Analysis of the entire coding sequence allowed identificatio n of 16 known mutations in CFTR gene. Fifteen chromosomes (31.2%) carried a mutation in CFTR gene and one allele carried two mutations. Three patients were homozygous or double heterozygous (<Delta>F508/Delta F508, Delta F508 /3849 + 10 kb C-->T, S1235R/G551D). The 5-thymidine allele was identified i n four children. Conclusion: These results indicate an higher frequency of CFTR gene mutatio ns in patients with borderline sweat chloride test results, compared to dat a reported in the general population. They lead to the recommendations for complete pulmonary and GI investigations in this group of patients, as well as assiduous care and medical follow-up.