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Cystic fibrosis is a genetic disorder that mainly affects the digestive systems and lungs. The exocrine glands like those secreting sweat, mucus, digestive fluids, etc are mainly affected. Abnormally thick mucus and salty sweat is produced which are the main cause of other symptoms in cystic fibrosis. It might cause early death due to multiple organ failure. It is most common in caucasian populations.

It was misdiagnosed as whooping cough,pneumonia,bronchitis,etc. But awareness traced back to 1700s. Discovered and studied 1930 onwards. The term cystic fibrosis was coined by Dr. Dorothy Andersen who published an article, "Cystic Fibrosis of the Pancreas and Its Relation to Celiac Disease: a Clinical and Pathological Study," in 1938 and hypothesized that CF was a recessive disease . 1952 Paul di Sant Agnese discovered abnormalities in sweat-thus sweat test. 1988 the first mutation for CF, F508 was discovered by Francis Collins, Lap-Chee Tsui and John R. Riordan.

In the world In the United States, approximately 30,000 individuals, 3000 Canadians, and 20,000 Europeans have CF. Occurs mostly in whites of caucasian decent. Less common in African Americans, Native Americans, and Asian Americans. 2500 babies are born with CF each year in the United States 1 in every 20 Americans is an unaffected carrier of an abnormal CF gene.

In India No statistics are found as it might be misdiagnosed. But according to the statistics of indians settled in US and UK, the incidence should be possibly 100,000 patients in India.


Lisa Bentley (Canadian Ironman triathlete)

Bob Flannagan(American performance artist, comic, writer, poet, and musician.)

GENERAL SYMPTOMS salty tasting skin poor growth and poor weight gain despite a normal food intake accumulation of thick, sticky mucus frequent chest infections coughing or shortness of breath Males can be infertile sometimes Digestive problems frequent affected newborn infant fails to pass faeces (meconium) protrusion of internal rectal membranes (rectal prolapse) Clubbed fingers and toes


SWEAT GLANDSSweat produced too salty(2-5 times more than normal) Thus more exhaustion or more sweating leads to salt loss and dehydration

RESPIRATORY SYSTEMNormally epithelial cells lining the respiratory tracts and the exocrine glands in the airways produce a thin slippery secretion called MUCUS. It provides a protective lubricant coating which captures microbes and dust from getting into the lungs and causing infections. This can be coughed out by the body with the help of cilia. In CF mucus produced is thick and sticky. This inhibits movement of cilia and thus plugs the airways and ducts and accumulates microbes. Causes infections.

Infections lead to inflammation which causes airways to get blocked and thus breathing problems result. This cycle continues,spreading the infection and thus damaging the the lungs(pulmonary exacerbation. Thus coughing, wheezing, pneumonia, bronchitis.

Normally, the exocrine glands of the pancreas and the digestive tract produce digestive enzymes to help in digestion inside the intestines. There are mucus producing glands present here also to help swift movement of the fluids through these tracts.

In CF the exocrine secretions are thick and they clog the pancreatic ducts. No passage of digestive enzymes to small intestine.
Poor digestion and absorption.

Malnutrition and weak. Rectal prolapse. Can also lead to pancreatic or intestinal inflammation. If pancreas impaired,islet cells affected. Thus diabetes can also occur. Vitamin absortion decreases causing severe weakness.

In men with CF sometimes vas deference in blocked or absent. Sperm production and transport affected. Thus almost 97% of men with CF are infertile(not sterile).

In women also conceiving might become a problem due to blockage of reproductory tracts by mucus but mostly they are not infertile.


Locus: 7q31.2 Gene Structure: The normal allelic variant for this gene is about 250,000 bp long and contains 27 exons. Coding Sequence (CDS): 4443 bp within the mRNA code for the amino acid sequence of the gene's protein product. Protein Size: The CFTR protein is 1480 amino acids long and has a molecular weight of 168,173 Da.

THE CFTR PROTEINIt is the cystic fibrosis transmembrane conductance regulator protein. The normal CFTR protein product is a chloride channel protein found in membranes of cells that line passageways of the lungs, liver, pancreas, intestines, reproductive tract, and skin. CFTR is also involved in the regulation of other transport pathways. It generally has five domains: two membrane-spanning domains (MSD1 and MSD2) that form the chloride ion channel, two nucleotide-binding domains (NBD1 and NBD2) that bind and hydrolyze ATP (adenosine triphosphate), and a regulatory (R) domain.

NORMAL FUNCTION OF CFTRRegulates movement of chloride ions out of mucus producing cells. Thus water follows by osmosis principle. So mucus thinned and slippery. CFTR functions principally as a cAMP-induced

IN CASE OF CFMutated CFTR cannot allow chloride ions to move out of the cells. Water cannot escape and thin the mucus. Thus mucus is thick and forms clogs.

Delta F508, the most common CF-causing mutation, occurs in the DNA sequence that codes for the first nucleotide-binding domain (NBD1). 508 is a deletion() of 3 nucleotides that result in the loss of the amino acid at the phenylalanine position at the 508th position of the protein.


When a CFTR protein with the delta F508 mutation reaches the ER, the quality-control mechanism of this cellular component recognizes that the protein is folded incorrectly and marks the defective protein for degradation. As a result, delta F508 never reaches the cell membrane. People who are homozygous for delta F508 mutation tend to have the most severe symptoms of cystic fibrosis due to critical loss of chloride ion transport. This mutation accounts for two-thirds (66-70%) worldwide and 90% of cases in United States,however there are 1400 other mutations that can produce CF.

Cystic fibrosis has anautosomal recessive inheritance Thus if both the parents are carriers, the child has 25% chances of becoming affected and 50% chances of being a carrier. Since autosomal, can occur in male and female populations alike.

Sweat glands are activated by a chemical called pilocarpine and mild electricity. Gauze pad or filter paper used to collect the accumulated sweat. Normal sweat chloride content <40 Sweat chloride concentration >60 is diagnostic for CF(for infants over 6 months.

Blood or buccal smear tested for F508 mutation 70% are homozygous for F508 mutation. Others have one F508 mutation and another form of CFTR mutation(heterozygous)


IMMUNOREACTIVE TRYPSINOGEN test is done in 2-3 days of the birth of the baby from blood sample. If levels high, CF positive.

Before pregnancy,blood test performed on healthy adults with family history of CF to determine whether they carry a recessive gene mutation that could cause disease in their children.

AMNIOCENTESISDone in the second trimester ,typically between the 15th and 18th weeks of pregnancy. thin needle is inserted into the uterus through the abdomen and a small amount of amniotic fluid is drawn out which is then analyzed for genetic and chromosomal abnormalities. CHORIONIC VILLI SAMPLINGDone in the first trimester, between the 10th and 12th week of pregnancy. thin needle inserted into the uterus through either the abdomen or the cervix Small sample of placenta is removed and analyzed for any genetic and chromosomal abnormalities.

Multiplex ligation dependent probe amplification(MLPA)

Quantitative fluorescent multiplex PCR

Chest Physical Therapy CPT also is called chest clapping or percussion. It involves pounding the chest and back over and over with hands or electrical percussor to loosen the mucus from lungs so that it can be coughed up. Exercise Not too much as salt content is lost due to sweating. Medicines Antibiotics are the main treatment to prevent or treat lung infections. They can be oral, inhaled, or intravenous (IV) antibiotics. Inhaled medicines generally given by aerosols or metered dose inhalers.(MDI) Nebulizers can also be used.

Medicines ctnd.
BRONCHODIALATORS-open airways,clear mucus. Eg-Albuterol MUCOLYTICS-Thins mucus. Eg-Pulmozyme ANTI-INFLAMMATORY- Reduces inflammations. Eg-steroids and non -steroidal Ibuprofen ANTIBIOTICS-Fights infection. Eg-Tobramycin

Oxygen therapy Lung transplants

Nutritional therapya well-balanced diet that's rich in calories, fat, and protein Oral pancreatic enzymes to help digest fats,proteins and absorb more vitamins. Supplements of vitamins A, D, E, and K High-calorie shakes A high-salt diet or salt supplements Oral pancreatic enzymes Antacids Surgery- of blocked intestines or pancreas.

Use of normal DNA to correct for the damaged genes that cause disease In the case of CF, gene therapy involves inhaling a spray that delivers normal DNA to the lungs The goal is to replace the defective CF gene in the lungs to cure or slow the progression of the disease More research is going on in this area to improve methods for transfer of therapeutic DNA into the affected patient with minimum or no risks

Through carrier screening if both parents are found to be carriers, the couple should go for genetic counseling before having a baby.

IVF techniques can be used to select healthy embryo for carrier parents. Awareness about the disease in general