TABLE OF CONTENTS

RESOURCES (MLA FORMAT)....................................................................................................................1

WHAT IS CF..................................................................................................................................................2
CAUSES..........................................................................................................................................................2
CFTR PROTEINS.......................................................................................................................................3
TYPES.............................................................................................................................................................3
SYMPTOMS.....................................................................................................................................................5
TESTING AND DIAGNOSIS..............................................................................................................................5
INHERITANCE................................................................................................................................................5
HOW IT AFFECTS AND COMPLICATIONS......................................................................................................6
TREATMENTS.................................................................................................................................................6
PROGNOSIS....................................................................................................................................................2

CYSTIC FIBROSIS INFORMATION

RESOURCES (MLA FORMAT)

o https://www.cff.org/research-clinical-trials/types-cftr-mutations#:~:text=There%20are%20five%20classes
%20of,different%20types%20of%20CFTR%20mutations.
o https://www.cff.org/sites/default/files/2021-12/Know-Your-CFTR-Mutations-Infographic.pdf
o https://rarediseases.info.nih.gov/diseases/6233/cystic-fibrosis#:~:text=CF%20is%20inherited%20in
%20an,referred%20to%20as%20a%20carrier%20.
o https://my.clevelandclinic.org/health/diseases/9358-cystic-fibrosis
o https://uihc.org/health-topics/how-cystic-fibrosis-affects-body
o https://www.news-medical.net/health/Cystic-Fibrosis-and-Infertility.aspx
o https://cffamilyconnection.org/10-basic-facts-about-cf/
o https://www.nhs.uk/conditions/cystic-fibrosis/#:~:text=Outlook,past%20the%20age%20of%2040 .
o https://www.yashodahospitals.com/diseases-treatments/cystic-fibrosis-syptoms-diagnosis-treatments/
o https://www.mayoclinic.org/diseases-conditions/cystic-fibrosis/symptoms-causes/syc-20353700
WHAT IS CF

https://my.clevelandclinic.org/health/diseases/9358-cystic-fibrosis

● Cystic Fibrosis is a progressive genetic disorder that causes the body to produce thick mucus.

○ Primarily affecting the respiratory system and digestive system. It affects the lungs, pancreas,
liver, gall bladder, and intestines.

● In healthy individuals, the secreted fluids such as sweat, mucus, and digestive juices are thin and free
flowing. In patients with CF, the fluid is sticky and thick. As a result, the tubes and ducts in these organs
become clogged.

● Cystic fibrosis is an inherited disease that causes sticky, thick mucus to build up in organs, including your
lungs and pancreas.

● If you don't have CF, the mucus that lines organs and body cavities, such as your lungs and nose, is
slippery and watery. If you do have CF, thick mucus clogs the airways and makes it difficult to breathe.

CAUSES

https://www.yashodahospitals.com/diseases-treatments/cystic-fibrosis-syptoms-diagnosis-treatments/

● Cystic fibrosis is genetic.

● People who have CF inherit two faulty genes, one from each parent. CF is said to be recessive because you
need to have two gene variants to have the condition itself.

● The CFTR gene that lies on chromosome 7 controls the movement of salts (sodium/chloride), thus
governing the movement of water and consistency of the secretions from these cells.

● Mutation of this gene predisposes to the poor movement of salt and water across the cells and thus causes
thickening mucus. The thickened mucus along the lining of the exocrine ducts and lumen are the hallmark
presentation of cystic fibrosis.

● Cystic fibrosis is a genetic disease that often passes from one generation to another.

○ The child may suffer from cystic fibrosis only if he/she receives gene error from both father and
mother

○ In case, the child receives a defective gene from just one parent, the child will then be a carrier
without any clinical presentation.

○ The gene carriers may possibly pass it on to their children.

CFTR PROTEINS

● The cystic fibrosis transmembrane conductance regulator (CFTR) gene contains the instructions for
making the CFTR protein. The protein controls the salt and water balance in the lungs and other
tissues.

● People who inherit two copies of the faulty gene lack effective CFTR proteins.

● This means that chloride ions build up in their cells instead of moving out through the channels and as
result water doesn’t move out of their cells to dilute the mucus on the surfaces of their membranes

● So, water moves into the cells by osmosis from the fluid surrounding the cells, making the mucus even
thicker and sticky

● c occurs in about 1 in 2400-2500 babies born to Caucasians

● Because CF is caused by a recessive allele, many people carry the mutation without knowing it.

● These carriers are phenotypically normal and usually have no idea that they are carrying the CF mutation.

TYPES

https://www.cff.org/research-clinical-trials/types-cftr-mutations#:~:text=There%20are%20five%20classes
%20of,different%20types%20of%20CFTR%20mutations.

● There are five classes of CFTR mutations: protein production, protein processing, gating, conduction, and
insufficient protein.

● Protein production: no functional CFTR is created

○ This mutation interferes with the production of CFTR

 ○ If the CFTR gene has a nonsense mutation, the protein building instructions contain an early stop
signal that causes the production of CFTR protein to stop prematurely.

○ Therefore, the cell begins to build the CFTR protein normally until it reaches the early stop signal.

○ The cell “thinks” that it’s reached the end of the instructions and stops the production too soon.

○ Because the cell stops reading the instructions before it finished making the protein, no functional
CFTR protein is produced.

● Protein processing

○ The most common CF mutation, F508del, is considered to be a processing mutation.

○ The F508del mutation removes a single amino acid from the CFTR protein. Without this, the
CFTR protein can’t stay in the correct shape. The cell recognizes that the protein isn’t the right
shape and disposes of it.

○ missense mutations can sometimes cause processing problems and therefore considered
processing mutations in those cases.

■ This occurs when a change in DNA letters causes an incorrect amino acid to be
incorporated into the CFTR protein. This leads to either a decrease in quantity of protein
at the cell surface (defective processing) and/or a decrease in the function of the protein
(defective gating or conduction)

● Gating

○ Gating mutations lock the gate in the closed position so that chloride can’t get through.

○ Medications like Kalydeco (ivacaftor) help people with gating mutations by forcing the gate of
CFTR channel to stay open. This enables chloride to move through the channel and reduces the
symptoms of CF.

● Conduction

○ Sometimes the change in one of the amino acids of CFTR means that even through the protein
makes the right 3-D chape, it doesn’t function as well as it should.

○ In order for CFTR to work correctly, chloride has to be able to move quickly and smoothly
through the protein’s channel.

○ Some mutations change the shape of the inside of the channel so that chloride cannot move
through as easily as it should.

○ This kind of mutation is called a conduction mutation.

● Insufficient:

○ This mutation results in a reduced amount of normal CFTR protein at the cell surface.

○ This happens for several reasons:

 ■ A limited amount of CFTR protein is produced; only a small number of proteins at the
cell surface works correctly; or normal protein at the cell surface degrades too quickly,
leaving small numbers of protein behind.

○ In each case, insufficient functional proteins at the cell surface produce only some, or residual,
function of the chloride channel.

○ It can be caused by several mutations, including missense and splice mutations

○ Some splice mutations interfere with the way the cell reads the DNA instructions for making a
protein. This can result in a limited quantity of normal CFTR protein reaching the cell surface,
which results in residual function

SYMPTOMS

https://www.mayoclinic.org/diseases-conditions/cystic-fibrosis/symptoms-causes/syc-20353700

 CF affects multiple organs, therefore, signs and symptoms may differ from person to person, depending on
the organ system involved. These include:
o A persistent cough that produces thick mucus (sputum)
o Wheezing
o Exercise intolerance
o Repeated lung infections
o Inflamed nasal passages or a stuffy nose
o Recurrent sinusitis
o Foul-smelling, greasy stools
o Poor wight gain and growth
o Intestinal blockage, particularly in newborns (meconium ileus)
o Chronic or severe constipation, which may include frequent straining while trying to pass stool,
eventually causing part of the rectum to protrude outside the anus (rectal prolapse)

TESTING AND DIAGNOSIS

https://www.yashodahospitals.com/diseases-treatments/cystic-fibrosis-syptoms-diagnosis-treatments/

https://my.clevelandclinic.org/health/diseases/9358-cystic-fibrosis#diagnosis-and-tests

 Depending on the organ system affected, the concerned specialists i.e., pediatricians, pulmonologists,
gastroenterologists, or physicians can diagnose the condition.
 The doctor performs the following tests for diagnosing cystic fibrosis:
o Medical history
o Physical examination
o Tests
 Sweat test to determine the salt content in sweat
 Screening test to check the levels of immune-reactive trypsinogen (IRT) chemical
 Genetic test to confirm the diagnosis
 Other tests are required
o Chest X-ray
 o Fecal fast test
o Lung function test

INHERITANCE

https://www.nhs.uk/conditions/cystic-fibrosis/#:~:text=Outlook,past%20the%20age%20of%2040

 To be born with cystic fibrosis, a child has to inherit a copy of the faulty gene from both of their parents.
 This can happen if the parents are "carriers" of the faulty gene, which means they don't have cystic fibrosis
themselves.
 It's estimated around 1 in every 25 people in the UK are carriers of cystic fibrosis.
 If both parents are carriers, there's a:

o 1 in 4 chance their child won't inherit any faulty genes and won't have cystic fibrosis or be able to
pass it on

o 1 in 2 chance their child will inherit a faulty gene from one parent and be a carrier

o 1 in 4 chance their child will inherit the faulty gene from both parents and have cystic fibrosis

 If one parent has cystic fibrosis and the other is a carrier, there's a:

o 1 in 2 chance their child will be a carrier

o 1 in 2 chance their child will have cystic fibrosis

HOW IT AFFECTS AND COMPLICATIONS

https://www.mayoclinic.org/diseases-conditions/cystic-fibrosis/symptoms-causes/syc-20353700

 The effects of cystic fibrosis may vary in every patient but the most common are:

o Damaged airways o Liver disease

o Chronic infections o Intestinal obstruction
o Growths in the nose (nasal polyps) o Distal intestinal obstruction syndrome (DIOS)
o Coughing up blood (hemoptysis) o Infertility in men
o Pneumothorax o Reduced fertility in women
o Respiratory failure o Thinning of the bones (osteoporosis)
o Acute exacerbations o Electrolyte imbalances and dehydration
o Nutritional deficiencies o Mental health problems
o Diabetes

TREATMENTS

https://my.clevelandclinic.org/health/diseases/9358-cystic-fibrosis

 Due to involvement of several organs, cystic fibrosis can be a complex disease to manage.
 Patients need immediate attention to respiratory implications such as, lung infection, thick sticky mucus;
and intestinal implications such as intestinal blockage, nutrition, and dehydration.
 Some of the commonly used modalities are:
 o Medications
o Airway clearance
 To remove the plugged mucous
o Pulmonology rehabilitation:
 To improve lung function and health, including activities like physical exercise, breathing
techniques and nutritional counseling. Rehabilitation may involve chest physical therapy,
energy conserving techniques and nutritional counseling. Rehabilitation may involve
chest physical therapy, energy conserving techniques and psychological counseling
o Lung transplant:
 Is suggested in severe cases if required
o Digestive care:
 Mucus-thinning medicines, oral pancreatic enzymes, and nutritional counseling.
Sometimes surgery may be necessary to remove intestinal blockages.

PROGNOSIS

https://my.clevelandclinic.org/health/diseases/9358-cystic-fibrosis#outlook--prognosis

 There is no cure for CF, and it cannot be prevented. However, new treatment methods help children
who have CF live well into adulthood and have a better quality of life.
 Therapies are most helpful when CF is diagnosed early, which is why newborn screening is so
important.
o These therapies include treating infections, trying to prevent weight loss, and seeing a CF
specialist frequently.
o The addition of cystic fibrosis transmembrane conductor regulator (CFTR) modulator therapy
at a young age seems to be very beneficial and may improve long-term health.
 According to information from the Cystic Fibrosis Foundation Patient Registry, more than half of
people born with CF between 2015 and 2019 are expected to live to age 46 or longer.
 People with atypical cystic fibrosis tend to have longer life expectancies than those with classic CF.