CF (Swest test)

Question

Hello, my daughter, born in 2004, has sweat test 58.5, ...55, but genetic testing were negative for CF (42 mutations). She is ill all the time with repeated sinusitis, wet prolonged caugh. Just ATB helped her. Her condition gets better after antibiotics treatment, but as soon as we start going out, to school etc., cough and other problems return within a week. Do You think she might have CF in older age? Thanks for an answer.

Answer

Hello,
The answer to your question isn´t an easy one. CF is sometimes rather difficult to diagnose and your daughter is probably one of the cases when it is so. Although she obviously has clinical symptoms of the disease, laboratory tests need to be carried out to determine that she really has CF. These should either show the result of 60 mmol/l of chlorides in her sweat, or prove the presence of two mutations which are known to cause CF.

It seems that your daughter doesn´t meet either of these. From your question we know, that the genetic test covered the 42 most frequent CF mutations. There are more than 1,700 mutations which cause CF. Most of them are very rare and they occur in one of over 70 000 CF patients that there are in the world. All mutations can't be routinely tested and only 50 most common mutations are subject of testing. Only in exceptional cases are complex and expensive genetics tests performed examining all known mutations. This is done with patients who show clinical symptoms of CF but whose sweat tests don´t have unambiguous results. Therefore, for your daughter, extended genetic investigation would be an option to clarify the situation.
The sweat test results that you mention in your question (assumed that it has been performed in a specialized center measuring the Chloride concentration in the sweat by a so-called pilocarpine ionotophoresis) are not positive nor negative, but lay in the "borderline area" (40-60 mmol/l chloride concentration of the sweat). In such cases, if extended genetic analysis does not help further, other diagnostic tests can be considered, e.g. measurement of the faecal elastase, the nasal potential difference (only in special centers possible) or further evaluation of the lung situation (lung function test, microbiological specimen, x-ray). Indeed, there are in some cases underlying mutations, that lead not to the classical picture of CF but to a milder form of CF down to so-called CFTR-related disorders; the symptoms may vary from a mild form of CF, e.g. with pancreatic sufficiency and mild lung disease, to sometimes only fertility problems in males.

We expect that other possible problem causes, such as failure of mucociliar clearence andimmune defects have been ruled out. Even if your daughter had CF, the sweat test wouldn´t play a decisive role in how the disease would develop. With similar diseases it is important for the patient to be regularly examined – once or twice a year - in a CF centre. As soon as any airway problems occur, intensive antibiotics treatment needs to be administered for at least two weeks and the dose should reach the upper limit of the recommended dosage. Inhalation and rehabilitation recommended by a doctor from your CF centre is equally important. Good cooperation with your CF centre and following all their recommendations is the most important factor influencing the disease's development.
We're sorry that we can't give you a more precise answer.
All best, ...

Dr. J. Brázová and Dr. Daniela d'Alquen

22.11.2011