Measurement of nasal potential difference in young children with an equivocal sweat test following newborn screening for cystic fibrosis.
BACKGROUND
A challenging problem arising from cystic fibrosis (CF) newborn screening is the significant number of infants with hypertrypsinaemia (HIRT) with sweat chloride levels in the intermediate range and only one or no identified CF-causing mutations.


OBJECTIVE
To investigate the diagnostic value for CF of assessing CF transmembrane conductance regulator (CFTR) protein function by measuring nasal potential difference in children with HIRT.


METHODS
A specially designed protocol was used to assess nasal potential difference (NPD) in 23 young children with HIRT (3 months-4 years) with inconclusive neonatal screening. Results were analysed with a composite score including CFTR-dependent sodium and chloride secretion. Results were correlated with genotype after extensive genetic screening and with clinical phenotype at follow-up 3 years later.


RESULTS
NPD was interpretable for 21 children with HIRT: 13 had NPD composite scores in the CF range. All 13 were finally found to carry two CFTR mutations. At follow-up, nine had developed a chronic pulmonary disease consistent with a CF diagnosis. The sweat test could be repeated in nine children, and six had sweat chloride values >or=60 mmol/l. Of the eight children with normal NPD scores, only two had two CFTR mutations, both wide-spectrum mutations. None had developed a CF-like lung disease at follow-up. The sweat test could be reassessed in five of these eight children and all had sweat chloride values <60 mmol/l. CF diagnosis was ruled out in six of these eight children.


CONCLUSIONS
Evaluation of CFTR function in the nasal epithelium of young children with inconclusive results at CF newborn screening is a useful diagnostic tool for CF.
CRCM and INSERM U845, Hôpital Necker, Faculté de Médecine Necker, Université René Descartes, Paris, France. isabelle.sermet@nck.aphp.fr
Isabelle
I
Sermet-Gaudelus
Emmanuelle
E
Girodon
Delphine
D
Roussel
Eric
E
Deneuville
Stéphanie
S
Bui
Frédéric
F
Huet
Marcel
M
Guillot
Rola
R
Aboutaam
Michel
M
Renouil
Anne
A
Munck
Marie
M
des Georges
Albert
A
Iron
Christel
C
Thauvin-Robinet
Isabelle
I
Fajac
Gerard
G
Lenoir
Michel
M
Roussey
Aleksander
A
Edelman
D002675:Child, Preschool; D002712:Chlorides / Q000032:analysis; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000502:physiology; D005500:Follow-Up Studies; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008564:Membrane Potentials / Q000502:physiology*; D009297:Nasal Mucosa / Q000503:physiopathology*; D015997:Neonatal Screening / Q000379:methods; D011379:Prognosis; D013542:Sweat / Q000737:chemistry; D014357:Trypsin / Q000097:blood
D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014357:Trypsin