Challenges in making the diagnosis of Cystic Fibrosis in the 21st century

Student thesis: Doctoral Thesis

Abstract

Cystic fibrosis (CF) is mostly diagnosed with a sweat test. Otherwise, a
genetic confirmation can be made if two CF-causing mutations are found on
each CFTR-allele (Cystic Fibrosis Transmembrane Conductance Regulator).
Insights in the basic defect of CF have resulted in the recognition of a wide
spectrum of disease severity related to CFTR-protein dysfunction. Apart from
the 'classic' CF patients, having pancreatic insufficiency and respiratory
disease resulting in a reduced life expectancy, other conditions with CFTRdysfunction
exist. Demarcation lines between these different entities are
blurred. This thesis aims to give insights in the barriers a clinician can face in
making a CF diagnosis.
Nasal potential difference (NPD) measurement can be helpful in diagnostic
inconclusiveness. In a semi-blinded study we showed that two different NPD
methods (needle vs abrasion) could equally discriminate CF from non-CF
individuals. The two methods were equally accepted by the study subjects,
concluding that the operator's preferred NPD-method may be used.
Little is known about rare CFTR-mutations (RM), present in only few CFpatients.
To investigate RMs in Belgium, a CF-registry study was conducted.
We found out that 6.5% of the Belgian CF patients carry at least one RM.
Sixty-four RMs were found, of which 21 had not been previously reported in
the global mutation database. As a group, these patients had milder disease
compared to controls with classic CF; however a wide spectrum in disease
severity was seen. To understand the disease liability of these RMs, a
prospective collection of electrophysiological and clinical data is needed. This
effort will enable to support or withdraw a CF diagnosis in patients with rare
mutations in the future
Date of Award26 Jun 2017
Original languageEnglish
Awarding Institution
  • Vrije Universiteit Brussel
SupervisorAnne Malfroot (Promotor), Yvan Vandenplas (Jury), Michel Deneyer (Jury), Inge Gies (Jury), Eef Vanderhelst (Jury), Jane C. Davies (Jury), Kris De Boeck (Jury) & Christiane Knoop (Jury)

Keywords

  • Cystic fibrosis
  • sweat test
  • diagnosis

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