DeltaF508 carrier

Question

Hello,

I have a son with CF and am a DeltaF508 carrier. I have severe mucus obstruction problems – both in the upper respiratory tract and gynaecological – with constant infections and frequent flatulence/stomach ache. I was already diagnosed with “hypersensitive brochial system” with significant values. I was prescribed an asthma spray even though I do not have asthma. My sweat test is negative. I was told that it is impossible for me to have CF. I nevertheless think that my medical troubles – which, by the way, are present in a direct line in my family tree without CF ever having been noticed – are related to the DeltaF508 gene. I also think that there is still considerable need for research. Is there a study I can participate in?

Answer

Dear questioner,

You are saying that you are a DeltaF508 carrier and mother of a child with CF. It seems that in your case, CF with a so-called heterozygosis (only one genetic defect verifiable) can be ruled out due to the negative sweat test. Furthermore, you are saying that you have been diagnosed with bronchial hyperreagibility (hypersensitive bronchial system), which is being treated with an “asthma” spray.

I can make out three “sub-questions” from your question:

1. You are not sure whether you might, after all, have a version of CF (mucous obstruction problems).

2. You are confused about whether you are getting the right therapy (asthma spray without asthma diagnosis).

3. You are asking about studies for healthy CF symptom carriers.

Ad 1.:
For people with clinical hints to CF (e.g. chronic productive cough, chronic bronchial mucous production, high susceptibility to infections, digestive problems, etc.) and heterozygous DeltaF508, but at the same time with negative sweat test (as in your case), additional diagnostics could be done to further preclude CF. This includes NPD (nasal potential difference measurement in the nasal mucous membrane) and ICM (intestinal current measurement with rectal mucus membrane biopsy). However, these two tests do not belong to the standard diagnostics and are offered only by a small number of hospitals in Germany in the context of research projects (e.g. at Heidelberg University Hospital or Berlin University Hospital). It will be best for you talk to your son’s CF doctor about the benefit of such tests for yourself, since he/she is in touch with you directly and will therefore be better able to asses your symptoms and initiate contact with the hospitals mentioned above if necessary.

Ad 2.:
It is quite possible that an “asthma” spray (I assume this is an agent that expands the bronchia or a drug that includes cortisone for inhalation) could be the right drug for bronchial hyperreagibility, even though you do not have asthma. In order to resolve your confusion about this, I recommend talking to a lung specialist.

Ad 3.:
We had a former question on this topic on the French website; please find the complete question and answer in the additional comment field below.
There have been some studies about the question of symptoms in carriers. In summary, carriers of one CF-mutation are generally well and deserve their name of "healthy carriers" even if the functioning of their CFTR protein is reduced. They are not at risk of developing severe respiratory impairment. However, slight respiratory or ENT symptoms might be a little more frequent.

I am currently not aware of any ongoing studies including healthy carriers of CF symptoms.

I hope this helps a bit and wish you and your son all the best.

Kind regards
Dr. Christina Smaczny

16.01.2012

Additional information on this topic was given in this French Q/A
Question
Hello,
At time of diagnosis, I was told that healthy carriers showed no symptoms. After meeting other parents of children with CF, I realize that many of us have chronic respiratory or digestive problems (asthma in my case). But I don't know if these observations are representative of all parents.
I wondered if a study was conducted on the subject.
That is a question I have been asking myself regarding the brothers and sisters as we do not know if they are carriers of one mutation or not.
Thank you in advance for your answer.
Answer
Hello,
A few studies have been conducted on parents of children with cystic fibrosis, also known as "obligate heterozygotes" because they carry a mutation in the cystic fibrosis gene (or CFTR gene).
In 1988, even before the discovery of the gene, Byard et al compared 280 parents of children with CF (obligate heterozygotes) to 280 non-carriers parents (parents of children with heart disease). "Healthy carriers" parents complained of wheezing more often but their lung function was comparable to that of parents with no children with CF.
In 2001, Castellani et al. compared 261 obligate heterozygotes to 201 controls, looking in particular for respiratory, digestive or ENT diseases. They found a slight increase in blood pressure in heterozygotes, as well as nasal polyps in heterozygote men. However the differences between the two groups disappeared when age was taken into account.
In 2005, Dr. Isabelle Sermet showed that the functioning of the CFTR protein was decreased in 52 parents of children with CF. In particular, their average concentration of chloride in the sweat test was higher than that of non-heterozygous subjects, but much lower than that of patients with CF. Among them, three complained of chronic sinusitis and 2 of asthma.
A study also published in 2005 (Wang et al) found that 36% of obligate heterozygotes (53/147) had chronic rhino-sinusitis based on their response to a self-administered questionnaire. A more detailed ENT examination confirmed the reliability of the questionnaire.
In summary, based on current knowledge, the parents of children with CF are generally well and deserve their name of "healthy carriers" even if the functioning of their CFTR protein is reduced. They are not at risk of developing severe respiratory impairment. However, small respiratory or ENT symptoms might be a little more frequent. In the case of more disabling respiratory symptoms, it is justified to achieve a complete genetic analysis in search of a second mutation in the CFTR gene, which would then indicate a mild form of cystic fibrosis.
Best regards.
Dr Dominique Hubert
10.11.2011