Cystic fibrosis: diagnosis and screening — formative SAQs

SAQ 1 (10 marks)

A 4-week-old girl is referred after a positive newborn bloodspot screen for cystic fibrosis: her immunoreactive trypsinogen was raised and the panel found one copy of ΔF508 (Phe508del). She is feeding well, gaining weight and looks entirely well on examination. Her parents are frightened and ask whether she "has cystic fibrosis". ^{[1] [2]}

1. What confirmatory test will you arrange, and how will you interpret the possible results? (4) ^{[1] [3]}
2. What does a single ΔF508 mutation on the screen mean for the diagnosis? (3) ^[2]
3. How will you explain the situation and plan to the parents today? (3) ^[2]

Model answer — SAQ 1

(1) Confirmatory test and interpretation (4). I would refer her to an accredited paediatric CF centre for a confirmatory sweat chloride test by pilocarpine iontophoresis, ensuring an adequate sweat sample. I interpret the result against reference thresholds: a chloride at or above sixty millimoles per litre is diagnostic of CF when confirmed on repeat testing, a value of thirty to fifty-nine is intermediate and needs extended CFTR genetics and repeat testing, and below thirty makes CF unlikely. Technique and sample adequacy matter, so testing is done in an accredited laboratory. ^{[1] [3]}

(2) Meaning of a single ΔF508 (3). A single CF-causing mutation on the screen makes her a confirmed carrier but does not, by itself, establish a diagnosis, because CF requires evidence of CFTR dysfunction — a raised sweat chloride, two CF-causing mutations, or an abnormal nasal potential difference. Her diagnosis therefore hinges on the sweat test and, if needed, extended gene analysis. If the sweat chloride is intermediate with fewer than two CF-causing mutations, she would be labelled CRMS or CFSPID rather than CF. ^{[2] [1]}

(3) Explanation and plan (3). I would acknowledge their fear and explain, in plain terms, that a positive screen is a flag for further testing, not a diagnosis, and that many screened babies turn out not to have CF. I would explain that we confirm with a sweat test at a specialist centre and use genetics, and that we will give clear results and a plan quickly. I would avoid both false reassurance and premature alarm, arrange the sweat test promptly, and offer written information and support. ^{[2] [1]}