Genes Matter
Cystic fibrosis (CF) is the most common severe recessive genetic disease in the Caucasian population, affecting about 1 in 4,500 people. The reason it is so prevalent is that one in 25 people is an asymptomatic carrier of the disease; this carrier rate is very high indeed.
CF affects several organs of the body, so it is considered multisystemic. Nowadays, thanks to early diagnosis and advances in medicine, the quality of life of those affected has improved.
What is cystic fibrosis?
Cystic fibrosis is a chronic hereditary disease that mainly affects the respiratory and digestive system, although it can affect most organs of the body.
This pathology is caused by an alteration in a gene (mutation) that affects the cells that produce mucus, sweat and digestive juices, causing them to become sticky and thick. As they become thicker, they are deposited in the different ducts of the organism, giving rise to the different signs of the disease.
Although it is a progressive disease that requires daily medical care, advances in early detection and treatment have made it possible to increase the quality of life and improve the prognosis of those affected, reaching a life expectancy of about 40 years.
Cystic fibrosis symptoms and complications
Signs and symptoms of cystic fibrosis vary among individuals and even within the same person over time.
As we have seen, this disease mainly affects the respiratory and digestive system, this is because the genetic variants responsible for cystic fibrosis affect the cells that line the tissues with exocrine and sweat function. The exocrine cells in people with CF produce abnormal thick, sticky secretions, which clog the ducts of the organs.
Patients with the disease usually develop symptoms as early as the first few months of life. A common sign that often alerts parents is a salty taste on the skin, which in some cases parents may notice when kissing their child. This is because the alteration of the sweat glands reduces the reabsorption of ions causing an increase in the concentration of chlorine and sodium in the sweat.
The most characteristic respiratory symptoms are:
The most characteristic digestive symptoms are:
In addition to the signs and symptoms related to the disease, people with CF may present complications such as infertility, which can affect both men and women, although it is less frequent in women. Patients may also present complications affecting other body systems such as nutritional deficiencies, diabetes, liver disease, nasal polyps, pneumothorax, osteoporosis or dehydration, among others.
There are cases in which people present with a mild form of the disease that may not manifest itself until adulthood.
Cause of cystic fibrosis: the importance of genetics
Cystic fibrosis is caused by an alteration in the CFTR gene, located on chromosome 7. This gene gives rise to a protein found mainly in the membrane of epithelial cells of glands located in the digestive, respiratory and genital tracts, as well as in sweat glands. This protein regulates the transport of electrolytes into and out of cells. Mutations in this gene result in an altered protein that cannot perform its transport function correctly, leading to an imbalance in ion concentration. Depending on the degree of alteration of the protein, the symptoms presented by the individual will be more or less severe.
As we mentioned, it is an autosomal recessive disease, that means two copies of each gene. In the case of recessive diseases, for the disease to develop, both copies of the gene must be affected.
When only one copy of the gene is altered, the person is said to be an asymptomatic carrier, since he/she does not have the disease, although he/she is at risk of transmitting it to his/her offspring. In Spain it is estimated that 1 in 25 people is a carrier of this disease.
Since the carrier frequency is very high, the chances of both members of a couple being CF carriers is also high. The problem with recessive diseases lies in the fact that generally the couple does not know that they are both carriers of the same disease, and in these cases the risk of their children developing CF is 25% in each pregnancy. This is why the incidence of CF is so high; in Spain it is estimated that 1 in 3,000 to 1 in 4,000 newborns have this disease.
There are more than 2,000 known mutations in the CFTR gene related to cystic fibrosis, although the most frequent is a deletion of the amino acid phenylalanine at position 508 (F508del), which accounts for more than 70% of mutations in Europeans of Caucasian origin. All the mutations described are classified into 6 classes according to their effect on the protein. The first 3 classes (class I, II and III) cause a total absence of the protein or a non-functional protein and the other three groups (class IV, V and VI) cause a partial alteration of the protein. It is essential to know the type of mutation in affected individuals because if they have two mutations belonging to any of the first three groups, their phenotype will be much more severe than those affected individuals with mutations classified in the other 3 classes.
How is the diagnosis of cystic fibrosis made?
In Spain, thanks to the neonatal screening or heel prick test performed on all newborns, about 91% of cystic fibrosis cases are detected in early stages of life. If you want to know more about this test you can read our article The newborn screening.
As it is a screening test, false positives and false negatives can occur, so it is always necessary to perform a diagnostic test to confirm the result. The most widespread diagnostic test is the sweat test, where the amount of chlorine in the newborn’s sweat is determined.
In addition, if the results confirm the diagnosis, a genetic test is usually performed to determine the type of mutation causing the disease. This is important because, as we have just seen, depending on the type of mutation the severity of the disease varies.
A few years ago the genetic study was oriented to analyze the most frequent mutations, however nowadays the analysis of the complete gene is more and more extended, which allows detecting any type of mutation that can cause the disease.
There are some cases where the symptoms of the disease are mild and the results of the sweat test are not conclusive, so the mildest forms of the disease may not be diagnosed. In these cases where there is suspicion, genetic testing can diagnose or rule out the disease.
What treatment is available for cystic fibrosis?
It is important to note that, although there is currently no cure for the disease, there are treatment options that can reduce the symptoms and complications associated with this pathology.
When a patient is diagnosed with CF, close monitoring is recommended and early management is performed to delay the progression of the disease.
Symptomatic treatment is multidisciplinary, based on 4 fundamental pillars:
The development of treatments for this disease continues to progress and recently there has been a breakthrough with the approval of a new drug aimed at improving the functioning of the protein damaged by the genetic mutation. This is an important milestone as this treatment is not a symptomatic treatment, but is aimed at solving the cause of the disease.
Despite this breakthrough, not all people with CF can benefit from this treatment, since it is a drug aimed at patients from 6 years of age who present at least one copy of the F508del mutation (the most frequent mutation associated with the disease).
As you can see, cystic fibrosis is a serious genetic disease that affects many people in the world. Genetic information is of vital importance, since it allows us to prevent its transmission, to detect the pathology early and to continue advancing in our knowledge, in order to be able to develop more effective treatments that allow us to slow down the progression of the disease and improve the quality of life of those who suffer from it.
At Veritas we are committed to proactive health care from the first days of life, offering tests aimed at preventing and adapting medical care to improve quality of life. For the youngest children we offer myNewborn, the perfect complement to the heel prick test, where in addition to looking for mutations in the gene that causes cystic fibrosis, more than 390 diseases are studied whose early management is key to avoid the onset of the disease or to reduce the severity of its symptoms.
For adults, Veritas offers myGenome, the most complete genetic prevention test that, in addition to informing you if you are a carrier of a disease such as cystic fibrosis, allows you to know your risk of actionable genetic diseases, your genetic response to drugs and much other important information to personalize your medical care. If you want to know more, do not hesitate to contact us.
Veritas Scientific Department
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