[MUSIC] Cystic fibrosis, also known as mucoviscidosis, is a lethal genetic disorder characterized by mutations in the CFTR gene. These gene codes for a chloride channel, which is expressed in epithelium throughout the body. And is involved in multiple organ functions such as in the lungs, and sinuses, in the pancreas, and in the biliary tract. Whenever a mutation has a functional impact on the general function, affected children suffer from severe respiratory problems and gastrointestinal tract problems as well. The clinical picture of cystic fibrosis is composed of a respiratory problems in the lungs and sinuses, combined with gastrointestinal tract problems. Among the respiratory problems, we can mention chronic sinusitis, chronic upper respiratory airway infections. And in the gastrointestinal tracts, people suffer mainly from chronic malnutrition and from pancreatic insufficiency. And men suffer as well from infertility, because of an abnormal vas deferens development. The prevalence of cystic fibrosis in populations of Northern European descent, is about 1 in 2500. And in those populations, about four persons are asymptomatic heterozygous carriers. Which means that they carry a single allele in the CFTR gene. Whenever parents are both carriers of these mutations, the risk of their child being affected by cystic fibrosis, is 1 in 4 or 25%. Cystic fibrosis is an autosomal recessive disorders, which necessitates that the child carries two mutated allele in the CFTR gene. So far, more than 2,000 mutations in these gene, have been described worldwide, and the most frequent one, present in about 70% of affected children, is F508del mutations. Which represent deletion of one amino acid in the encoded channel. The disease causing mutations are resulting a defective chloride transport which, as a consequence, may lead to a reduced channel expression or an increased degradation of the channel. Or a dysfunction of the channel, or they may also be several of those problems combined. People affected with cystic fibrosis have reduced life expectancy. But thanks to major improvements in therapeutics and preventive measures, their life expectancy has substantially increased during the past decades. And so for a median median survival in most countries, has reach 50 years. Between 2000 and 2010, the mortality decline in people affected with cystic fibrosis in the US, was about 1.5 % per year. Studies have noticed that depending on the number of copies of the F508del mutation, survival is differential. The mortality rate ratio of people carrying one mutation, as compared to those carrying two mutations of F508del is 0.82, that is 18% reduced mortality. And those who carry zero of those mutations, have a mortality rate ratio of 69%, so about 30% reduced mortality, as compared to those who carry two mutations. There are three main screening tests for cystic fibrosis. One is IRT, immunoreactive trypsinogen, which represent the measurements of an enzyme coming from the pancreas. The second one is genetic testing. So measuring mutations in the CFTR gene, and the panel of those tests may differ from country to country, according to people origins. And the third one, which is also a confirmatory diagnostics test, is the sweat chloride test, which represents the gold standard. Newborn screening programs for cystic fibrosis, have started in the early 70s. And so far, many many countries have now implemented those universal screening programs. In 2015, more than 15 European countries now implement universal newborn screening for cystic fibrosis. And those programs have seen that an early diagnosis of cystic fibrosis leads to better diagnosis in affected children. Because treatment may be initiated earlier, as well as preventive measures to avoid repetitive respiratory infections. Multiple different newborn screen programs have been adopted throughout the world. That is various combinations of the screening tests, that I have just described, have been applied in different regions of countries. That is, programs may combine ROT tests as a first tier with a second ROT test. Or they may follow the first ROT test with a genetic screening. Or they may also combine ROT test with a second one, followed by CFTR mutation screening in the population. In all those conditions, the diagnosis needs to be confirmed by a sweat chloride test. What are the rational for a cystic fibrosis screening in the general population, is disease has a poor prognosis with reduced life expectancy. Early treatment, thanks to early diagnosis as a consequence of screening, allows a better prognosis in the patients. In particular, people who have been diagnosed via a newborn screening program, have improved nutritional status, a better growth, a fewer hospitalizations, decreased the life-threatening complication, and earlier diagnosis and treatments. The risk of cystic fibrosis screening, however, exist in that some newborns, falsely labelled as being negative, and others falsely labelled as being positive. False negatives of course leads to a delayed diagnosis. That is, children are considered as not having cystic fibrosis during the newborn screening, whereas they do indeed have cystic fibrosis. And then the diagnosis will only be made when they start developing signs and symptoms of the disease. And this will result in delayed management of the children. Those who are false positive, that is they are labelled as having cystic fibrosis within the frame rate of the newborn screening program, but they later on turned out to be negative. The risk is that this may lead to anxiety in the parents, which may persist even if they are reassured by a negative confirmatory tests. In conclusion, cystic fibrosis is a life-threatening autosomal recessive disorders, involving lung, pancreas, and biliary tract problems, that can be diagnosed via universal newborn screening. Several regions and countries around the world, have implemented such programs during the past decades. And they have shown that early detection of cystic fibrosis, thanks to those screening program, is able to improve the life expectancy and the quality of lives of people diagnosed with cystic fibrosis. [MUSIC]
