Cystic fibrosis is a recessive genetic disorder caused by a mutation on the 7th gene, where the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) seems to be missing or have limited function .The CFTR protein is made of 1480 amino acids, some of the mutations cause the ATP to become unable to bind and open the ion channel. However, the most common mutation is the F508del which is the deletion of 3 nucleotides, which causes the loss of the 508th amino acid, which is Phenylamine, this results in the misfolding of the protein, this explains the limited function of the mutated version of the gene. The CFTR gene helps the body maintain and regulate the water and salt levels in the mucus, when the CFTR is damaged or missing causing the sodium ions channels to remain open, the elevated level of sodium ions in cells draws chlorine ions and water out of the mucus into the cells, causing the mucus to be thick and sticky . This genetic disease is uncurable and the life expectancy is 50, however some patients manage to live to their 80’s.
Cystic fibrosis effects many areas of the body such as the respiratory system, reproductive system, and digestive system. Beyond the physical implications this disease has on those affected, it poses intense emotional challenges to themselves and their loved ones. Approximately 105,000 people have been diagnosed with this disease across 99 countries. In the UK, 1 in 25 is a carrier, meaning they have a copy of the mutated version of the CFTR gene but don’t present the symptoms themselves. Being a carrier has no effect on one’s health. Furthermore, there is also another type of cystic fibrosis, which is called atypical cystic fibrosis and is usually diagnosed much later in life , it is a milder form of the sickness, affecting only 1 organ such as lung disease, recurrent pancreatic or nasal polyposis .
Symptoms of cystic fibrosis were observed years before it’s discovery. In the early 20th centuary doctors began noticing patients, especially children, displaying digestive and respiratory problems. In 1938 Dr. Dorothy Andresen , an American pediatrician, decided to conduct autopsies on children who had previously displayed symptoms, she found cyst's in the pancreas and created the term ‘ cystic fibrosis of the pancreas’. In 1989 the CFTR gene was identified on chromosome 7 and researchers found that the mutation of this gene was what causes the disease in an individual. Between 1990s-2000s researchers and scientist focused on identifying the different mutations in the CFTR gene. After figuring out the CFTR gene’s mutation, researchers began working on developing targeted different treatments and therapies. The following years saw great improvements in the developments of treatments.
Since cystic fibrosis is a recessive genetic disease, this means that both parents must be carriers, for their child to be able to inherit the two mutated copies of the gene. Cystic Fibrosis is almost always detected by the age of 2, with most people getting diagnosed at birth . There are many different tests physicians perform to identify the disease. One of which is newborn screening, many different countries all around the world test a small blood sample from a newborn to see if the baby has high levels of immunoreactive trypsinogen (IRT), which could be a sign the baby has the disease. If elevated levels of IRT is detected the newborn will undergo many additional tests to confirm the diagnosis. Moving on, the sweat test measures the concentration of salt in the sweat, as those affected with cystic fibrosis have high salt level due to the impaired function of the CFTR channel. Genetic testing is done to confirm the diagnosis and it can help determine the exact mutation present, providing crucial information, helping the affected individual get the best treatments possible for their specific situation.
As I have previously mentioned the body systems most affected by cystic fibrosis are the digestive, respiratory and reproductive system .Cystic fibrosis produces a thick, sticky mucus which then causes it to plug up tubes, and passageways resulting in a plethora of different issues. In the respiratory system, the mucus is so thick that the cilia is unable to move the mucus and waft it upwards towards the throat to remove it, this means that the mucus accumulates in the lungs , blocking airways, so that less air reaches the alveoli’s , reducing the steepness of the concentration gradient and limiting gas exchange . Furthermore, another problem that arises due to the buildup of mucus in the respiratory system is the fact that microorganisms are not effectively removed from the lungs, leading to lung infections. Those affected also have a cough .
The digestive system also has many different problems in those individuals with CF. For one, the tube connecting the pancreas and small intestine is blocked with mucus. This prevents digestive enzymes from reaching the small intestine meaning the digestion of food is heavily reduced, causing many key nutrients to not be absorbed by the body. Moreover, the buildup of mucus can cause cysts to grow in the pancreas , inhibiting the production of enzymes reducing digestion. Additionally, the lining of the intestines is coated in thick mucus, inhibiting the absorption of nutrients into blood. A lot of babies affected with the disease have meconium ileus- which is the blockage of the intestines – this occurs shortly after birth. A type of diabetes known as cystic fibrosis related diabetes ( CFD) is a common complication of CF. A person with cystic fibrosis’s blood pressure can become too high, as the blood glucose levels is controlled by the hormone insulin, which is made by the pancreas. Since the pancreas’s duct is blocked the insulin doesn’t enter the bloodstream, causing blood glucose levels to remain high. Liver disease can occur due to cystic fibrosis. This occurs when the mucus builds up blocking the bile duct in the liver. As the bile cannot leave, the liver becomes inflamed, this produces scarring. In very rare conditions a child with CF may have rectal prolapse where the end of the bowels comes out of the anus.
Cystic fibrosis also affects the reproductive system. In men, the tubes of the testes are blocked, preventing sperm from leaving this is referred to as congenital absence of the vas deferens.Approximetly 97% of men with cystic fibrosis are infertile because of congenital absence of the vas deferens . In women, the thick mucus in the cervix can prevent sperm from reaching the oviduct to fertilize an egg.
Although there is no cure to cystic fibrosis there have been numerous developments over the years for treatments to help alleviate the pain and reduce the number of complications. Many different medicines can be used to treat the disease, such as antibiotics to treat and prevent lung infections. Medicines such as domase alfa and hypertonic saline help make the mucus thinner and easier to cough up,. Bronchodilators are taken to widen the airways, making breathing easier by allowing more air in and moving mucus out. Bronchodilators are inhaled through a device called the metered- dose inhaler, bronchodilators can also be administers through a nebulizer or dry powder inhaler. There are also types of drugs that help reduce the levels of mucus in the body such as ivacaftor. Moving on, exercise can help clear the mucus. Physiotherapists can teach those living with the disease techniques to help keep the lungs clear , such as autogenic drainage which is a series of controlled breathing techniques designed to help clear the mucus and airway clearance devices use air pressure and vibrations to help remove mucus as well. As the pancreas doesn’t work well, it is vital that a high calorie diet, with a lot of protein is taken alongside digestive enzymes to aid with digestion. In severe cases, heart and lung transplants might be needed, although they carry risks of serious implications, getting a transplant dramatically improves the quality of life for those with severe cases.
Gene therapy has the potential to cure cystic fibrosis in the future. Through this method, a piece of DNA with the correct copy of the CFTR gene is given to an affected person’s cells, the existing cells can use the new copy of the CFTR gene to make normal CFTR proteins. However, this is not permanent, and the person will have to be treated with gene therapy every few months for it to become effective.
In conclusion , cystic fibrosis is a serious genetic disease which has many implications on an individual’s life, both mentally and physically. It is essential to raise awareness and advocate to continue researching the disease, in hopes of finding a cure.
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