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Original article
Does extensive genotyping and nasal potential difference testing clarify the diagnosis of cystic fibrosis among patients with single-organ manifestations of cystic fibrosis?
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  1. Chee Y Ooi1,2,3,
  2. Annie Dupuis4,5,
  3. Lynda Ellis2,
  4. Keith Jarvi6,
  5. Sheelagh Martin2,
  6. Peter N Ray7,8,9,
  7. Leslie Steele8,9,
  8. Paul Kortan10,
  9. Tanja Gonska1,2,
  10. Ruslan Dorfman7,
  11. Melinda Solomon1,11,
  12. Julian Zielenski7,
  13. Mary Corey4,5,
  14. Elizabeth Tullis10,12,
  15. Peter Durie1,2
  1. 1Physiology and Experimental Medicine, Research Institute, The Hospital for Sick Children, Toronto, Canada
  2. 2Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Canada
  3. 3Discipline of Paediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales and Department of Gastroenterology, Sydney Children's Hospital Randwick, Sydney, Australia
  4. 4Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, Canada
  5. 5Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
  6. 6Division of Urology, Mount Sinai Hospital, Toronto, Canada
  7. 7Departments of Genetics and Genome Biology, Research Institute, The Hospital for Sick Children, Toronto, Canada
  8. 8Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Canada
  9. 9Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Canada
  10. 10Department of Medicine, University of Toronto, Toronto, Canada
  11. 11Department of Paediatrics, Division of Respirology, Hospital for Sick Children, Toronto, Canada
  12. 12Division of Respirology, Keenan Research Centre of Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada
  1. Correspondence to Dr (Keith) Chee Y Ooi, Discipline of Paediatrics, School of Women's and Children's Health, Sydney Children's Hospital Randwick, High Street, Randwick, NSW 2031, Australia; keith.ooi{at}unsw.edu.au

Abstract

Background The phenotypic spectrum of cystic fibrosis (CF) has expanded to include patients affected by single-organ diseases. Extensive genotyping and nasal potential difference (NPD) testing have been proposed to assist in the diagnosis of CF when sweat testing is inconclusive. However, the diagnostic yield of extensive genotyping and NPD and the concordance between NPD and the sweat test have not been carefully evaluated.

Methods We evaluated the diagnostic outcomes of genotyping (with 122 mutations included as disease causing), sweat testing and NPD in a prospectively ascertained cohort of undiagnosed patients who presented with chronic sino-pulmonary disease (RESP), chronic/recurrent pancreatitis (PANC) or obstructive azoospermia (AZOOSP).

Results 202 patients (68 RESP, 42 PANC and 92 AZOOSP) were evaluated; 17.3%, 22.8% and 59.9% had abnormal, borderline and normal sweat chloride results, respectively. Only 17 (8.4%) patients were diagnosable as having CF by genotyping. Compared to sweat testing, NPD identified more patients as having CF (33.2%) with fewer borderline results (18.8%). The level of agreement according to kappa statistics (and the observed percentage of agreement) between sweat chloride and NPD in RESP, PANC and AZOOSP subjects was ‘moderate’ (65% observed agreement), ‘poor’ (33% observed agreement) and ‘fair’ (28% observed agreement), respectively. The degree of agreement only improved marginally when subjects with borderline sweat chloride results were excluded from the analysis.

Conclusions The diagnosis of CF or its exclusion is not always straightforward and may remain elusive even with comprehensive evaluation, particularly among individuals who present at an older age with single-organ manifestations suggestive of CF.

  • Cystic Fibrosis
  • Bronchiectasis
  • Paediatric Lung Disaese
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