An Introduction to Genetic Diseases: Cystic Fibrosis


Hello readers! Sorry for being a week late with a post. Last week got a little hectic and I didn’t have a chance to sit down to write it.

This week’s question comes from one of my oldest and closest friends, Steve, who asks “I have Cystic Fibrosis. Can you explain the sources of my symptoms and what treatments are being developed?”

Let’s first start with what causes the disease. Cystic fibrosis (CF) is a autosomal recessive genetic disease, which means that both the mother and father must either have active CF (two copies of the mutated gene) or be carriers (have one functional copy of the gene and one CF mutation) to even have the possibility of creating a child with the disease. Carriers do not have CF symptoms but when paired with another carrier can have a 25% chance of creating a baby with CF. Like with many genetic diseases, one would think that the odds of two people being carriers coming together at random would be fairly low, but that is sadly not the case for CF.   Roughly 4% of the Caucasian population worldwide have active CF or are carriers, and smaller but still significant percentages of other races also have the mutation. This makes CF a major disease affecting the western world, most especially in Europe.

The mutated gene in question codes for the CFTR, or cystic fibrosis transmembrane conductance regulator, protein. While the specifics of this protein are not important, what is important is what it does. the CFTR protein controls the concentration of ions in mucous and other secretions.  The most important ions in question are chloride (Cl-) and sodium (Na+), though others such as thiocyanate (SCN-) and iodide (I-) also play a role. The ability of the body pump these ions into and out of its secretions is what determines its viscosity (by the transport of water based on osmotic pressure– the greater the number of ions present, the more water will want to travel to the mucous). Because the CFTR protein is mutated, the secretions become extremely thick and sticky by virtue of dehydration. There is some debate as to the exact mechanism of this dehydration, but for these purposes the exact mechanism isn’t important.

While it may seem on the surface to be fairly manageable, since to many mucous only exists in the nose and throat, the reality is much more sinister. CF affects many different body systems. Let’s run through them briefly.

  • Respiratory system (lungs and sinuses): Mucous, as we all know from being sick, is a vital part of the body’s immune defense. Mucous in the nose, sinuses, throat, and lungs capture and expel (via little moving fingers called cilia) particles, fungi, bacteria, and viruses that could otherwise take root and damage the sensitive breathing spaces. Unfortunately, because CF secretions are so thick, they are difficult to expel. That turns the mucous from a blessing to a curse by trapping unwanted organisms but then providing them a fertile ground to reproduce. CF sufferers are often very sensitive to respiratory illnesses, even ones not normally seen in otherwise healthy people since the thick secretions can allow normal bacteria to grow uncontrolled. These infections can progress to serious lung and cardiopulmonary (heart and lung system) problems after repeated infections. The sinuses also take a beating from chronic infections, including overgrowth of tissue (“polyps”) that reoccur frequently and chronic pain and sinus pressure. 
  • Digestive system: The thick secretions extend to the digestive tract as well. In fact, the term “cystic fibrosis” actually refers to scarring (“fibrosis”) and cyst (“cystic”) formation around the pancreas. The thickened secretions apply mainly to two digestive organs: the pancreas and liver. The pancreas is a key part of the digestive system responsible for breaking down food as well as releasing the hormones insulin and glucagon, among others. This scarring and cyst formation is due to a backing up of abnormally thick secretions from the pancreas (“digestive juice”); this process can be very painful and over time result in pancreatitis (inflammation of the pancreas). With the juice backed up, the ability to digest food properly is severely diminished (digestive juice helps break down proteins, fats, and carbohydrates), those with CF can suffer from malnutrition and vitamin insufficiencies. Damage to the pancreas can also cause CFRD, or cystic fibrosis related diabetes, due to the destruction of the insulin producing cells in the pancreas. The liver is the main detoxifying organ and excretes bile (via the gall bladder), which is use to help break down fats. In CF, the  liver can excrete thicker than normal bile, causing a similar back up as occurs in the pancreas. In this case, cirrhosis (scarring) of the liver can occur with the resulting loss of liver function. Thick mucous along the interior of the intestines can also causes feces to travel more slowly, which could possibly result in an intestinal blockage. But, the primary digestive consequences arise from damage to the pancreas and liver.
  • Other physical signs: One of the methods of testing for CF as a child is called the sweat test, which measures the ion concentration (saltiness) of the sweat. CF causes an abundance of salt (sodium and chloride together) in the sweat. Stunted growth due to malnutrition, including diseases associated with digestive vitamin deficiencies (ie. bone issues from lowered vitamin D, clotting disorders from lack of vitamin K, etc.) also frequently occurs. Clubbing of the fingers, which is common in lung diseases where oxygen intake is chronically low, is often present as well. Finally, sterility tends to be common amongst CF sufferers (though not universally) due to structural, nutritional, and/or secretory limitations.

Granted, that list sounds pretty rough all together, and it is. But, luckily CF is not one mutation but rather a collections of various mutations across a spectrum. Some are more severe and affect more body systems than others. Some only have mild progressive respiratory involvement and some have wide ranging effects across the body. The most common CF mutation, known as ∆F508, accounts for roughly 70% of all CF cases worldwide. It has many of the signs and symptoms listed earlier, including sterility in males. But well over 1000 other mutations can cause the range of CF symptoms. For example, A455E is considered a milder form, with preserved pancreatic function and more slowly progressing respiratory symptoms. Each mutation represents a different change to the very long CFTR gene.

Insofar as treating CF, there are a few angles being attacked in an attempt to resolve or work around the mutation of the CFTR gene. Some of them are mutation specific, some are more general. For example, a drug currently under investigation called Ataluren can help resolve mutations like G502X, which is what is known as a non-sense mutation (where a change in the code causes a premature stoppage of protein creation, resulting in an incomplete protein), by allowing the premature stop to be skipped. Because the code is otherwise intact save for the premature stop, the drug can allow theoretically for a functional protein to be created and the CF symptoms to be reduced accordingly. Another promising area is gene therapy. Gene therapy involves the use of a manufactured carrier virus that infects the target cells and replaces the mutation with a functioning version. This would theoretically be effective for all types of CF, though the nature of its delivery is limiting to its usefulness (ie. breathing in an aerosol only helps the respiratory tract). Time will tell if these types of treatments pan out. In the mean time, treatments are largely reactive and concentrate on thinning and expelling secretions, antimicrobial administration to fight against infection, and periodic surgeries to address blockages and any serious complications (ie. lung transplant). Clearly, more permanent solutions are necessary to truly treat the disease.

Hope this helps, Steve! Thanks for the question! As always, feel free to submit questions you want answered!

Till next time,


EDIT: A few people have let me know that there is a CF awareness walk happening in Huntington Beach on May 4. The event information can be found here. I encourage everyone reading this to donate and/or walk  to show your support not just for CF patients but for all those struggling with genetic diseases.

EDIT: It has been brought to my attention that the word “mutation” can be considered an offensive word when used to describe the source of a patient’s disease. I just want to let you all know that my use of the word mutation in this article is purely from a scientific stand-point and not in any way meant to offend or degrade the quality of people afflicted with genetic disorders. Every single person on this planet has genetic variations, some small and some very big. This article is meant to spread knowledge and awareness, not single out any particular group as different or somehow unequal.


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