The severity of cystic fibrosis

Question

My question is how you can determine the severity of CF. I know it starts with a mutation but which symptoms, how many airway infections do occur. I know this is a difficult question but can you say something about it.

Answer

The severity of symptoms in patients with CF is partially determined by the type of mutation in the CFTR gene. These mutations will impact on the production and function of the CFTR protein that functions as a channel for the transport of salt (chloride ions). We distinguish 5 categories of mutations. Every CF patient carries 2 mutations, not necessarily of the same mutation class. With a class 1 mutation, no CFTR protein is been made. In the class 2 mutations, the abnormal protein will be destroyed and will not make it to the cell surface. In type 3 mutations the protein is present in the cell surface but cannot be activated. In type 4 mutations the channel doesn’t function sufficiently and in type 5 mutations there is too little protein present. Patients carrying 2 class 1 to 3 are usually have severe disease. These patients have the classical symptoms of early and severe lung infection, malabsorption, clearly abnormal sweat test and infertility. Diabetes and liver problems usually only occur at a later age. Patients carrying at least one class 4 and 5 mutation have a milder disease course. That means the symptoms start at later age, are associated with less severe damage in the organs and a times improved survival. These patients usually have a normal digestion and do not have to take pancreatic enzymes. At times patients have very mild disease symptoms and present just with male infertility. On the other hand, there still is a wide range disease severity in patients with exactly the same mutation. Therefore we know that other genetic factors , we call them ‘modifier genes’, will also determine the disease severity. In addition environmental factors such as age at diagnosis, intensity of treatment, contact with smoke play an important role. We can say a lot about groups of patients, but it is very difficult to give a good prognostic indication for an individual patient. In addition a patient with classic disease and a mild course at a young age cannot be guaranteed that this mild course will continue throughout his life.

Kind regards,

Dr. Mieke Boon
Prof. K De Boeck

28.04.2011