Study objectives: Cystic fibrosis (CF) is one of the
most common inherited diseases among whites. Since the cloning of the
CF transmembrane conductance regulator (CFTR) gene, a
number of studies have focused on associations between the genotype and
phenotype in CF. This had led to the progressive identification of new
groups of patients, including those who have mild lung disease and
those who have normal sweat chloride values (< 60 mEq/L). The aim of
the present work was to provide information on the genotype and the
phenotypic characteristics of children with intermediate-range sweat
chloride test results.
Patients and results: We
focused on children referred to the pulmonary department for various
types of pulmonary disease and who had several sweat chloride test
results with median values in the range of 40 to 60 mEq/L. Twenty-four
patients over a 10-year period were enrolled (mean age, 4.8 years).
Respiratory manifestations at initial evaluation included recurrent
bronchitis, 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 Haemophilus 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 identification 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
(ΔF508/ΔF508, ΔF508/3849 + 10 kb C→T, S1235R/G551D).
The 5-thymidine allele was identified in four children.
Conclusion: These results indicate an higher frequency of
CFTR gene mutations in patients with borderline sweat
chloride test results, compared to data 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.