Please note: While some information will still be current in a year, other information may already be out of date in three months time. If you are in any doubt, please feel free to ask.

Borderline sweat test results/genetic testing

Hello, I am a woman of English descent living in Finland and my family has a history of cystic fibrosis. I have a history of nasal polyps, recurrent pancreatitis, recurrent sinus infections and intestinal ileus. I also have a fatty liver and pancreas divisum. My gallbladder was removed because of sludge in 2001. I had recurrent bronchitis and pneumonia as a child, but my respiratory symptoms have since disappeared.

I discussed the possibility of atypical cystic fibrosis with a doctor in Finland, and she reluctantly allowed me to take a sweat test. The result was 44, which they consider completely normal here in Finland (anything under 60 here is normal, and only results over 80 are considered affirmative). They refuse to do any genetic testing.

Is it possible to travel to another country for genetic testing?

Thank you.
Dear Questioner

Many thanks for your question.
At first, some general things on the performance of a sweat test have to be said in order to be able to judge a certain value of the result. According to existing guidelines (Farrell et al. in the Journal of Pediatrics 2008; 153:S4-S14 “Guidelines for Diagnosis of Cystic Fibrosis in Newborns through Older adults: Cystic Fibrosis Foundation Consensus Report”), the sweat test should be performed using the so-called “pilocarpine ionotophoresis” to measure the chloride concentration in the sweat, sweat chloride is the only analyte on which a diagnosis of CF should be based (not NaCl concentrations, conductivity or osmolality measurements). So please make sure, that the sweat test has been performed according to this procedure in an experienced center doing many of those sweat tests per year. If this is the case, the following values pertain (also consistent with the report of the CF Foundation Consensus Report on Diagnosis of CF):
A sweat chloride of at least 60 mmol/L indicates a positive result and between 40 and 60 mmol/L indicates an equivocal result. Values of 39 mmol/l or below are not consistent with the diagnosis of CF, however, even in those individuals, it is still possible (even if it is very rare) to detect 2 CF-causing mutations (Farrell, 2008). Even more complicated is the further diagnostic procedure, if the sweat chloride values are in the intermediate range (if your sweat test has been performed according to the above mentioned guidelines, a value of 44 mmol/L chloride in the sweat would belong to this group). First of all, one could repeat the sweat test in an experienced center. If the values are then still in the intermediate range, let me cite the mentioned guidelines for the ongoing procedure:
“Individuals with sweat chloride values in the intermediate ragte should undergo extensive CFTR mutation analysis (=genetic testing) (i.e. expanded panel of CFTR mutations, evaluation for deletions, or gene sequencing):
a. In the presence of 2 CF-causing mutations, a diagnosis of CF can be made
b. Individuals with no or 1 CF-causing mutation and clinical findings suggestive of CFTR-dysfunction (i.e. obstructive azoospermia (=male infertility), bonchiectasis, or acute, recurrent or chronic pancreatitis) may be diagnosed with a CFTR-related disorder, depending on their clinical picture or family history and are at risk for CF.”
If the situation still cannot be totally clarified by the genetic analysis (even if extended genetic investigation has been performed) other tests should be performed at a CF Center to clarify the situation (detailed clinical assessment, exocrine pancreatic function tests, respiratory tract cultures, imaging of lung and pancreas, pulmonary function tests and measurement of the nasal potential difference etc.)
Given that you have a family history of CF and you are also describing some symptoms that can be associated with CF or are indicative of a CFTR-related disorder and your sweat test result is seemingly in the intermediate range, a genetic testing for CFTR mutations would be the next and important step to make a diagnosis. To know, if you are a carrier of one, two or none CFTR-mutations is not only important for the clinical management, but it is even more important for your own family planning (which mutations are present that could be inherited to the next generation) and the family planning of other members of your family (if you carry a mutation, who has probably also inherited this from your parents could give it to their offspring). Therefore it may be a good idea to discuss the option of further testing again with the clinicians that are treating you. Failing that, you can always ask for a second opinion from an independent clinician in your home country. As for the question of travelling to another country for genetic testing this would probably be a question of coverage of the costs for the genetic investigation by your health insurance. If the clinicians in your country refuse a genetic testing, I would assume that you could go yourself to a genetic center in your country, to have this investigation done, the only questions is then, who covers the costs. The same would be abroad: is your health insurance paying any treatment abroad? Therefore I would recommend to clarify this with your insurance first, how and where a genetic investigation can be covered that is obviously necessary to clarify the situation.
Hope this has helped you further,

Yours sincerely
Dr Lisa Kent, Belfast, Northern Ireland
Dr Daniela d'Alquen, Wuerzbug, Germany
The answer is edited by: PhD Lisa Kent