CF Diagnosis

Question

Has a CF diagnosis from the heel prick test ever been wrong?Both parents did have gene mutations and same faulty genes detected in child. A sweat test has never been carried out and from 3 weeks all the usual preventative treatment has been done. To date 4 years down the line nothing has ever been cultured or no other symptoms of CF appeared. I do appreciate it is highly unlikely the diagnosis is not correct and symptoms can develop later in life but this is just something I would like to know. A sweat test is going to be done soon.

Answer

Dear Questioner
Thankyou for your question regarding screening and detection of CF.
No diagnostic test can have 100% sensitivity and specificity and there is always some possibility of false positives and false negatives. Sensitivity and specificity will vary from screening programme to screening programme as they are not all the same. However most newborn screening programmes have now included a two-tiered system with IRT and CFTR mutation analysis. The CHOPIN study from the Netherlands which uses IRT/PAP(pancreatitis associated protein) & CFTR mutation analysis felt its specificity to be greater than 99.9% and sensitivity to be around 95%.(1)
However in the case you have described you have noted that genetic testing has confirmed both parents to be known carriers and the child has been identified as having the same genetics. This would make it extremely unlikely that there has been an error in diagnosis.
The symptoms that a young child will have with CF vary widely and are dependent on genetics and environmental factors. Those with milder mutations with pancreatic sufficiency are less likely to have significant symptoms in childhood and may only develop symptoms as they get older. With over 1800 CFRT mutations now identified the clinical implications of all are not always clearly established.
Your question notes that the child has not had a sweat test. The sweat test remains a gold standard for diagnosing or confirming CF. If there is any doubt over the diagnosis sweat testing should be the next step in the investigation process for this child. If this proves inconclusive which it can do in a small number of cases (some milder mutations may be associated with equivocal or normal sweat chloride) then repeat genetic testing could be carried out.
I hope you have found this information helpful. Regards Dr Laura Jenkins CF Paediatric Associate Specialist

References:
1.Improving test properties for neonatal cystic fibrosis screening in the Netherlands before the nationwide start by May 2011 2. Martina C. Cornel, Johan J. P. Gille, J. Gerard Loeber, Annette M.M. Vernooij-van Langen, Jeannette Danhert Roelse and Piet A Bolhuis; J Inhert Metab Dis 2012 July 35(4):635-640
2.European best practice guidelines for cystic fibrosis neonatal screening Castellani C, Southern KW, Brownlee K, Dankert Roelse J, Duff A, Farrell M, Mehta A, Munck A, Pollitt R, Sermet-Gaudelus I, Wilcken B, Ballmann M, Corbetta C, de Monestrol, Farrell P, Feilcke M, Perec C, Gartner S,Gaskin K, Hammermann J, Kashirskaya N, Loeber G, Macek M Jr, Mehta G, Reiman A, Rizotti P, Sammon A, Sands D, Smyth A, Sommerburg O, Torresani T, Travert Vernooiji A, Elborn S
J Cystic Fibros 2009 May 8(3)153-73

22.10.2012

The answer is edited by: Laura Jenkins