In this essay, I will discuss cystic fibrosis a recessive genetic illness, which is characterised by respiratory, digestive and reproductive problems. Firstly, I will explain what cystic fibrosis is, how it is caused and the available treatments.
Cystic fibrosis (CF) is an autosomal recessive disorder, which is characterised by a build up of mucus primarily in the lungs and airways, making breathing difficult. Cystic Fibrosis has a high prevalence in individuals of Western European descent, having an Incident rate of 1 in 2000-3000. The prevalence rate of cystic fibrosis amongst other world populations is much lower1 .
In terms of aetiology, cystic fibrosis is an autosomal recessive disorder, meaning that two copies of the faulty gene are required in order for an individual to have the illness. The cystic fibrosis gene is found in chromosome seven, in section q31. This gene codes for a protein, known as the cystic fibrosis transmembrane conductor protein (CFTR). The CFTR protein operates as a Chloride ion channel in the cell membranes of mucus producing glands, sweat producing glands and glands which produce digestive enzymes. It is a member of a group of proteins known as transporter ATPases, and has a structure, which helps greatly with its function. It consists of five domains. One regulatory domain, two are nucleotide binding folds (NBF), which attach to ATP and hydrolyse it and two transmembrane domains (these function as the chloride ion channel) 2.
This protein is a Chloride ion transporter, i.e. it works by transporting chloride ions across the cell membrane. This occurs firstly, by activation of the regulatory domain (involving phosphorylation of the domain), then binding of ATP to the nucleotide binding sites; resulting in the hydrolysis of ATP. When the ATP becomes hydrolysed, the chloride ion channels opens, and chloride ions move across the channel1. “The transport of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucus”4. The CFTR gene also controls other membrane channels which move sodium into and out of cells. A mutation, which occurs in this gene, will cause the resultant protein to be ineffective at its job, resulting in thick mucus being produced.
The majority of mutations in cystic fibrosis (70%) are due to the deletion of three neighbouring bases which results in the loss of the 508th codon. This codon codes for the amino acid phenylalanine therefore, this mutation is known as F5084.
As cystic fibrosis is a recessive illness, two copies of the faulty gene are required in order for an individual to have the disease. If an individual inherits one faulty gene from one parent and one normal gene from the other parent, they will not have the illness as approximately 50% of their CFTR will be normal; this amount is sufficient to insure normal transport of chloride ions across the cell membrane3.
Due to the wide variety of mutations, the illness affects different people in different ways i.e. two people both suffering from Cystic Fibrosis will not have same symptoms, although their symptoms will be similar and there may be overlap. For example, one person may have sinusitis whilst the other does not.
Mutations in cystic fibrosis affect the function of the protein in many ways. Some mutations may stop the protein from reaching the cell membrane, whilst other mutations result in the protein operating incorrectly 1.
In Cystic fibrosis, the pancreas and lungs are most seriously affected. Due to the build up of mucus which clogs the lungs and airways, individuals with cystic fibrosis are at a high risk of lung infection as it enables bacteria to grow, resulting in recurrent infections5. These recurrent infections cause scarring of the lung tissue. Chronic lung disease, by far is the most common cause of death in patients with cystic fibrosis, as lung tissue worsens each year due to lung infections6. Cor pulmunale may also develop in patients with cystic fibrosis. This is when patients develop cardiac failure secondary to lung disease1.
Most patients with cystic fibrosis also suffer from malnutrition. This is due to two main reasons: firstly, the thick mucus lines the intestines resulting in impaired absorption of nutrients as digestive enzymes are incapable of accessing the food which needs to be digested. Secondly, as the pancreatic duct is blocked by mucus, digestive enzymes which are produced in the pancreas and aid in the digestion of nutrients, are unable to leave the pancreas, meaning nutrients cannot be absorbed. This results in individuals having light, greasy stools6. Cystic fibrosis can also cause sinusitis, pancreatitis, diabetes, nasal polyps, haemoptysis, liver cirrhosis6 and males becoming sterile, due to “congenital bilateral absence of the vas deferens (CBAVD)”1.
In relation to potential treatments, there are currently many treatments available for cystic fibrosis, each treatment tackling one of its symptoms. Ideally, as cystic fibrosis is a genetic illness, the best treatment, would be gene therapy or injecting individuals suffering from cystic fibrosis, with the healthy version of the CFTR gene7. However, currently none of these options are available.
The current available treatments for cystic fibrosis include chest therapy. This involves laying or sitting the individual with the illness in specific positions and percussing the chest in these different positions. The aim of this treatment is to dislodge the mucus from the lungs. Individuals with CF are also encouraged to cough, in order to release the mucus. Individuals with CF, are also encouraged to partake in exercise as exercise is thought to helps loosen the mucus in the lungs.7
Other treatments for cystic fibrosis include antibiotics, which are taken to treat and prevent lung infection, bronchodilators, which help widen the airways and mucolytics which make the mucus thinner7.
In terms of malnutrition, this is treated by taking vitamin tablets, and having a diet which is high in proteins and calories, but low in fats. Individuals with cystic fibrosis are also prescribed pancreatic enzymes which help in the digestion of food as their pancreatic ducts are blocked.7
In conclusion, cystic fibrosis is a hereditary recessive genetic illness, which results in a build-up of mucus in the airways and other organ systems, resulting in a wide variety of symptoms including diabetes mellitus, lung infection, infertility, mal-absorption and malnutrition. Currently, the available treatments for cystic fibrosis tackle the symptoms and not the root cause. Although these treatments have proved to be successful and have greatly helped those suffering from cystic fibrosis, they are not life sustaining and have not eradicated the illness. In my opinion, further research should be done, which is geared towards a potential cure for cystic fibrosis.