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Measurement of nasal potential difference in young children with an equivocal sweat test following newborn screening for cystic fibrosis
  1. Isabelle Sermet-Gaudelus1,
  2. Emmanuelle Girodon2,
  3. Delphine Roussel1,
  4. Eric Deneuville3,
  5. Stéphanie Bui4,
  6. Frédéric Huet5,
  7. Marcel Guillot6,
  8. Rola Aboutaam1,
  9. Michel Renouil7,
  10. Anne Munck8,
  11. Marie des Georges9,
  12. Albert Iron4,
  13. Christel Thauvin-Robinet5,
  14. Isabelle Fajac10,
  15. Gerard Lenoir1,
  16. Michel Roussey3,
  17. Aleksander Edelman1
  1. 1CRCM and INSERM U845, Hôpital Necker, Université René Descartes, Paris, France
  2. 2Service de Génétique Moléculaire, Hôpital Henri Mondor, France
  3. 3CRCM, Hôpital Pontchaillou, France
  4. 4Génétique Médicale et CRCM Pédiatrique, Hôpital Pellegrin, France
  5. 5CRCM, Hôpital du Bocage, France
  6. 6CRCM, Hôpital Robert Bisson, France
  7. 7CRCM, Hôpital de Saint Pierre, France
  8. 8CRCM, Hôpital Robert Debré, France
  9. 9Service de Génétique Médicale, Hôpital Arnaud de Villeneuve, France
  10. 10CRCM, Hôpital Cochin, France
  1. Correspondence to Isabelle Sermet-Gaudelus, CRCM, Hôpital Necker-Enfants Malades and INSERM U845, Faculté de Médecine Necker, Université René Descartes, 156 rue de Vaugirard, 75730 Paris, France; isabelle.sermet{at}nck.aphp.fr

Abstract

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.

Objectives 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 ≥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.

Conclusion 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.

  • CFTR
  • CFTR-related disorder
  • cystic fibrosis
  • nasal potential difference
  • newborn screening
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Footnotes

  • Funding Supported by Assistance Publique des Hôpitaux de Paris, Vaincre La Mucoviscidose and ABCF Mucoviscidose.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Necker-Enfants Malades Institutional Review Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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