Clinical phenotype and genotype of children with borderline sweat test and abnormal nasal epithelial chloride transport.
BACKGROUND
The diagnosis of cystic fibrosis (CF) is based on a characteristic clinical picture in association with a sweat chloride (Cl(-)) concentration greater than 60 mmol/L or the identification of two CF-causing mutations. A challenging problem is the significant number of children for whom no definitive diagnosis is possible because they present with symptoms suggestive of CF, a sweat chloride level in the intermediate range between 30 and 60 mmol/L, and only one or no identified CF-causing mutation.


OBJECTIVE
To investigate the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in the airways of children with intermediate sweat tests and inconclusive genetic findings in correlation with clinical phenotype and genotype.


METHODS
We developed a composite nasal potential difference (NPD) diagnostic score to discriminate patients with CF from non-CF patients. We tested NPD in 50 children (age, 6 mo to 18 yr) with equivocal diagnoses and correlated the NPD diagnostic score with clinical phenotypes and genotypes.


RESULTS
Fifteen of the 50 children had NPD scores in the CF range. Eight of the 15 carried two CFTR mutations compared with only 5 of the 35 children with normal NPD scores (P = 0.01). They were significantly younger at evaluation and had recurrent lower respiratory tract infections, chronic productive coughs, and chronic Staphylococcus aureus colonization significantly more often than the 35 children with normal NPD results.


CONCLUSIONS
Evaluation of CFTR function in the nasal epithelium of children with inconclusive CF diagnoses can be a useful diagnostic tool and help clinicians to individualize therapeutic strategy.
Centre de Référence et de Compétence en Mucoviscidose, Hôpital Necker-Enfants Malades, Paris, France. isabelle.sermet@nck.aphp.fr
Isabelle
I
Sermet-Gaudelus
Emanuelle
E
Girodon
Dorota
D
Sands
Nathalie
N
Stremmler
Vera
V
Vavrova
Eric
E
Deneuville
Philippe
P
Reix
Stéphanie
S
Bui
Frédéric
F
Huet
Muriel
M
Lebourgeois
Anne
A
Munck
Albert
A
Iron
Veronika
V
Skalicka
Thierry
T
Bienvenu
Delphine
D
Roussel
Gérard
G
Lenoir
Gabriel
G
Bellon
Jacques
J
Sarles
Milan
M
Macek
Michel
M
Roussey
Isabelle
I
Fajac
Aleksander
A
Edelman
D000293:Adolescent; D015415:Biomarkers; D016022:Case-Control Studies; D002648:Child; D002712:Chlorides / Q000378:metabolism; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D005838:Genotype; D006801:Humans; D007223:Infant; D009297:Nasal Mucosa / Q000378:metabolism*; D010641:Phenotype; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013542:Sweat / Q000737:chemistry
D015415:Biomarkers; D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator