Cystic fibrosis: diagnosis and screening — branching viva

Opening

Examiner: A well-looking 5-week-old is referred with a positive newborn screen for cystic fibrosis — raised trypsinogen and one ΔF508 mutation. How do you approach this? [1]

Candidate: I would treat a positive screen as a flag for confirmatory testing, not a diagnosis. My first step is prompt referral to an accredited paediatric CF centre for a confirmatory sweat chloride test, supported by CFTR genetic analysis. I would take a history for any early features and a family history, examine her, and, crucially, explain to the anxious parents that many screened babies do not turn out to have CF while we confirm the result quickly. [1] [2]

Branch 1 — confirming the diagnosis

Examiner: How is the sweat test done, and how do you interpret it? [3]

Candidate: Sweat is stimulated by pilocarpine iontophoresis, collected, and its chloride concentration measured in an accredited laboratory with an adequate sample. I interpret the result against thresholds: a chloride below thirty millimoles per litre makes CF unlikely, thirty to fifty-nine is intermediate and needs genetics and repeat testing, and sixty or above is diagnostic when confirmed. An inadequate sample gives an unreliable result, so technique matters. [3] [1]

Examiner (probe): What are the full diagnostic criteria for cystic fibrosis? [1]

Candidate: Diagnosis needs a trigger plus objective evidence of CFTR dysfunction. The trigger is a clinical feature, a positive newborn screen, or a sibling with CF. The evidence of CFTR dysfunction is a sweat chloride at or above sixty millimoles per litre, two CF-causing mutations, or an abnormal nasal potential difference. A single mutation makes a carrier, not a diagnosis. [1] [2]