complete genetic test_pancreas divisum

Question

[coordinators comment: the Q/A presented here is a summary of 3 questions from the same parent; we had a fourth former question from this parent, where in the answer the probability of suffering from CF/CFTR-related disorder or being healthy carrier was discussed in detail. This Q/A can be found under the following link: http://ecorn-cf.eu/index.php?id=65&L=0&tx_expertadvice_pi1[showitem]=1618&tx_expertadvice_pi1[search]=uncertain%20cystic]

I bring back a previous subject about an uncertain CF diagnosis, with a few additional informations.
My daughter is 11 years old and she was diagnosed in Iasi with CF as a result of two sweat tests (the first – 68, the second - 62). These tests were made after previous fasting (no food and no water), first they collected the blood, they took the X-ray, and they evaluated the pulmonary function and after that she had to eat something and drink some water (all of that happening in maximum 30 minutes). From what I know, the patient must be hydrated for this test. This fall we got, by chance, at Grigore Alexandrescu Hostpital in Bucharest, where she repeated the test using the pilocarpine ionotophoresis method. I mention the fact that the device and method differed from those used in Iasi: they collected the sweat in a small tube and they weighed it and the result was 42. The MRI revealed pancreas divisum and the lungs are fine for the moment (until now she only had rare and mild colds). The doctors in Bucharest infirmed the CF diagnosis.
The screening test for mutations revealed polimorphism of IVS8-5T- allele [coordinator put in this information from a former question: intron 8 poly-T-TG: 5T-11TG/7T-11TG].
We payed the complete sequencing CFTR test, performed by PCR, bidirectional sequencing, MLPA. The people at the laboratory we contacted said they are doing the CFTR gene sequencing and this covers 98% of mutations. The tests did not detect any mutations in the CFTR gene, just polymorphisms without clinical relevance, the conclusion was that is unlikely the child has cystic fibrosis. Please advise me what to do in the future about the Pulmozyme? Is it necessary? I remember you that pancreas divisum was diagnosed by MRI. I understand that she should continue the treatment for pancreatic disease but I am confused about Pulmozyme. She did not have any pulmonary disease. Thank you very much for your understanding and patience.

Answer

Dear questioner,
Sequencing is a more complicated method, which can indeed detect 98-99% of mutations. So with a certainty of 98% it seems from your information that there is no other CFTR mutation besides the already by you mentioned polymorphism 5T-11TG. This is at most a “healthy carrier state” as even in combination with a CFTR-mutation the 5T-11TG polymorphism is highly unlikely to cause disease. The only valid sweat test value is the one taken by pilocarpine ionotophoresis, 42mmol/l chloride in the sweat is however just above the negative level and has to be judged as borderline, which is striking, as one would expect a rather negative result, so an underlying mild dysfunction of the CFTR channel cannot 100% excluded even if the diagnosis of CF can be ruled out.
As your daughter does not suffer from CF and has according to your information no pulmonary problems, the therapy with Pulmozyme does not seem to be necessary anymore. However, it would be recommendable to be under constant supervision of your pediatrician to have an eye on the lung health and to react with prompt therapy if any problems might occur. Of course your child's doctor will recommend further treatment for the pancreatic disease diagnosed. We wish you and your child all the best and we are happy that the diagnosis of cystic fibrosis was denied.
Sincerely yours,
Prof.Dr.Pop and Dr. Daniela d'Alquen

25.06.2012