With an occurrence of about 1 out of 3,000 newborns in the Caucasian population, Mucoviscidosis, also known as Cystic Fibrosis (CF) is one of the most “common” rare genetic diseases. It causes mainly chronic respiratory tract infections because of the accumulation of thick mucus blocking the airways. Various treatments can be used to mitigate the symptoms, but there is no known cure for CF. Hence, the disease is an important medical burden for patients, leading to shortened life expectancy.
CF is due to mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR), an ion-channel protein that carries water and chloride ions in and out of epithelial cells. As for other rare diseases, making a correct diagnosis is central to pinpoint the illness among other more common syndromes and ensure appropriate care. This is especially true in adults, as CF is usually diagnosed at birth thanks to blood tests looking for high levels of immunoreactive trypsinogen, an enzyme accumulating in the pancreas because of the disease. These newborn screenings (NBS) are standard practices in countries with developed healthcare systems but are not systematic worldwide and can always be prone to false negatives.
For these reasons, this recent article from Seminars in Respiratory and Critical Care Medicine by Peter Barry (Manchester Adult Cystic Fibrosis Centre) and Nicholas Simmonds (Adult Cystic Fibrosis Centre, Brompton Hospital London) investigates the challenges in diagnosing cystic fibrosis in adults, with the purpose of making the medical community more aware about late-in-life CF presentation and current diagnostic pathways.
As mentioned, the most common CF symptom in adults is recurrent respiratory tract infection, but abnormal stool, nasal polyps caused by sinus congestion and male infertility might be indicative of the disease. Family history can be screened too, as well as high levels of salt in sweat, due to CFTR defective chloride reabsorption in sweat glands.
Once patients are referred to CF-specialized units by their physician, multiple diagnostic tools are available. Nasal Potential Difference and Intestinal Current Measurements screen for CFTR function as a transmembrane conductance regulator, ie. its ability to manage electric charges distribution across cell membranes. However, in addition to rectal biopsies for ICM, these tests require specific equipment and qualified operators, which limits their generalization.
Assessment of CFTR dysfunctions by genetic means is thus another available option. Indeed, more than 2’000 genetic alterations have been reported for CFTR. Those mutations of varying clinical consequence (VCC) can range from slight alteration leading to mild symptoms, to complete deletion of the protein abilities. Reliable molecular profiling is critical because the diagnosis also needs to integrate the autosomal recessiveness of the disease, meaning that the variant state of both chromosomes has to be taken into account.
Thanks to 4bases dedicated panel, it is possible to screen for virtually all CFTR variants using a straightforward PCR-based workflow, providing medical professionals with hands-on genetic testing solutions for their patients. In the upcoming area of personalized medicine, those kinds of tests can help provide an adequate diagnosis for rare diseases with varying phenotypes such as Cystic Fibrosis.
Barry PJ, Simmonds NJ. Diagnosing Cystic Fibrosis in Adults. Semin Respir Crit Care Med. 2023 Jan 9. doi: 10.1055/s-0042-1759881. Epub ahead of print. PMID: 36623819.