CF diagnosis in adulthood

Question

Dear,

I recently got the diagnosis of CF at the age of 25.

After performing a sweat test (result: gray area) and a DNA test, I seem to be genetically homozygous F508del. With this form you would expect serious complaints.
Given the late diagnosis, I only suffer from mild CF.
Here is my question: is it possible to have a mild form of CF even if a genetically severe form is expected? And how can this be explained?

Thank you

Answer

Dear,

Thank you for this interesting question.

As you undoubtedly know, cystic fibrosis, or CF, is a congenital condition. The basic defect lies in an absent or defective chloride channel in the wall of the cell (for more detailed information see related questions). This is because the genetic code, for the production of the chloride channel, contains an error (= mutation). This error is present since the birth, but symptoms can sometimes only show up at later age. The more the chloride channel is damaged (e.g. if it is completely absent), the sooner the symptoms are usually present. CF symptoms can already start during the first days of life with the development of meconium ileus (= complete blockage of the small intestine due to sticky stools) or during the first months, with poor weight gain despite adequate caloric intake. Both symptoms are the result of a malfunction of the pancreas. Also respiratory symptoms can develop at a very young age. In other cases, the diagnosis of CF is only made later in life, and sometimes only in adulthood because the symptoms are milder and only become apparent at a later age.

Several genetic defects (= errors in the genetic code, called mutations) are the basis of CF. Today, more than 1800 different errors that can lead to CF have been described. Some of these mutations have only a limited impact on the function of the chloride channel, so that the expression of the disease is much milder than what is seen with the so called "severe mutations”. Patients who suffer from this 'mild' or 'atypical' form of cystic fibrosis, often get the diagnosis of CF at a later age, because the symptoms specific to this disease are less pronounced. Examples are often chronic sinusitis, nasal polyps, recurrent bronchitis. In some cases the diagnosis is made because of male infertility.
Those adults did not get the disease during their life, the genetic defect is present from birth. The symptoms however only show up at a later age.

To respond specifically to your question: Yes, also at an older age symptoms of cystic fibrosis can become apparent. In these cases, the symptoms are usually milder and less pregressive than in the classic form of CF. Additionally: even between patients carrying the same mutation, there is a big difference in severity of illness. It is unusual, but not impossible, that the diagnosis of homozygous F508del is only made in adulthood. It this situation, we expect that there are other ‘genes than the CF gene that have a protective role, which explains why symptoms the symptoms are less pronounced.

For personal medical advice we refer you to your doctor or you can make an appointment in an accredited CF center.

Prof. K. De Boeck

23.12.2013