always sick daughter

Question

My daughter is since birth a sweet ‘mommie’s’ child. She was breast fed for one year (with some food supplements) but after that, started to eat less and less and be more and more tired and listless. At the age of 17 months, she even got dehydrated and needed to be admitted to the hospital. The doctors did one test after the other until a sweet test revealed an elevated salt content. The repeat test was even worse. It think the first one was 33 and the next one was 40. They took blood for DNA and 2 weeks later they stated: ‘We did the test for the most common mutations and since she doesn’t have any of these, we think it is psychological. ‘This felt like getting a slap in my face. They never said anything anymore about her runny nose and ears. Since half a year I am very worried. My daughter looks healthy but she is very small: she is almost 2 years old and only weighs 8kg. In the mean time she had surgery on her ears, grummets were inserted and here adenoids where removed. She is not getting better, she still has very little appetite.
Don’t you think that she should be checked for another type of CF?

Answer

Thanks for your question. We do understand that you are worried. You want to know what is wrong with your child and you want to know if she does or does not have CF.
Of course an internet site is not a substitute for a consultation. To know what is wrong with your child, you need to go back to your doctor. Only he can come to a final conclusion.
Here we can only give you general information about the types of CF and how you can check whether somebody is suffering from CF or not.
CF is a disease with a variable symptom pattern: from very severe typical disease (with poor digestion and chest problems from infancy on) to mild atypical forms presenting in adulthood with milder symptoms. Please read more about this under the section “diagnosis”.
Several tests can be done to make the diagnosis of CF. The most commonly used test is the sweat test. Here it is important for correctly interpretation of results, that the test is performed in an experienced center and that it measures the chloride concentration in the sweat by a method called "pilocarpine ionotophoresis". In people with typical cystic fibrosis (early onset of symptoms, fat malabsorption, infections of the airway) this test is clearly positive with a sweat chloride higher than 60 mmol/L. In the meantime we know that some people with a lower sweat chloride value (between 30 and 60 mmol/L and in very rare cases even lower than 30 mmol/L), still may have some form of CF. A sweat chloride between 30 and 60 mmol/L can thus be the reason for further testing, if the child has symptoms that are typical for CF (e.g. poor digestion). Sweat results lower than 30 mmol/L make CF really very very unlikely.

A second diagnostic test for CF is mutation analysis, the DNA test that you refer to. More than 1500 different mutations (or errors) in the CFTR-gene have been found in people who suffer from the disease cystic fibrosis. Some of these errors are very rare and have only been found in a few people. People with CF always carry two abnormal CFTR genes (one inherited from the father, one inherited from the mother). Some of these errors lead to worse consequences than others. Please read more in the section on ‘genetics’.
When testing for CF mutations, only the 36 most common mutations are evaluated. Still, with this test nearly 90% of the CF-patients in the Netherlands or Belgium have their mutations demonstrated. It is however possible that with this routine mutation test only one mutation is found in a person with CF, if the second mutations is a rare mutation and not included in the ‘standard mutation panel’. To be certain that there is no second mutation, the whole gene needs to be sequenced. If no abnormalities are found on sequencing, CF is very unlikely. But even this complete sequencing of the gene does not detect all types of CF, because some patients lack a piece of the gene or have changes hidden very deep in the gene (deep in the intron, the non coding regions of the gene).

If there still is doubt, an additional test can be done that directly evaluates the function of the chloride channel. This test can be done in the nose (nasal PD test) or in the intestine (intestinal current measurement, ICM). You can also read more about these tests under the section ‘diagnosis’.

In conclusion, milder forms of CF do indeed exist in which the classical tests will be less clear cut and whereby additional testing is necessary. In the Netherlands and in Flanders specialized CF-centers have the necessary knowledge and equipment to evaluate these problematic cases.

Kind regards
Prof. Dr. K. De Boeck, Prof J Dankert-Roelse

05.12.2011