Cystic Fibrosis – What and Why?

Cystic fibrosis is an inherited, genetic disorder caused by the transmission of defective genes from both parents to their children. It is caused due to the mutation of CFTR gene, expanded as Cystic fibrosis transmembrane conductance regulator. Mutation results from unrepaired damage to DNA or RNA, genetic material of an organism due to influence of extreme variations in either internal or external environment. Over 1,600 different CFTR mutations have been identified till now. Chronicity of Cystic fibrosis is a major concern and is associated with recurrent pulmonary infections and pancreatic dysfunction.

Incidence and Genetics:

Cystic fibrosis is of two types, Classic and Nonclassic, Classic being the most common type. It is noted that there are two severe mutations on CFTR gene in case of Classic Cystic fibrosis and one severe, one mild to moderate mutation in Nonclassic form. The disease is common among Caucasians and more than 90% affected belong to them. The Incidence is 1 in 3,000 among Caucasians [mainly Europeans ] or Ashkenazi Jews, one in 8,000 among Hispanics[ White Americans ], 1 in 15,000 among African Americans and 1 in 32,000 among Asians. Cystic fibrosis is usually diagnosed by newborn screening or in early childhood.

Cystic fibrosis is autosomal recessive disorder which means the child is affected with the disease only if both parents have the genetic trait, parents need not be symptomatic cases, if both are carriers or if one is carrier and one is symptomatic or if both are symptomatic the child can be affected. The common scenario seen is when both parents are carriers; in this case each child of the parents will have 25% chance of getting the disease. Millions of Americans have the defective gene but they do not express the symptoms as they are carriers and carry single defective gene. When two such carriers give birth to a child, baby might be symptomatic.

Cause of Cystic fibrosis:

The cause is mutation of CFTR gene, the most common mutation is “Delta f508” which leads to deletion of amino acid Phenylalanine at 508th position on the protein of the nucleotide, part of gene. This particular mutation is the cause of 80 to 90% affected in United states and around 70% cause for worldwide cases.

What happens in Cystic fibrosis?

CFTR gene codes for a protein which is present on the outer membrane of epithelial cells which is present in all exocrine glands of the body especially sweat glands, lungs and pancreas. This protein created by CFTR gene acts as a channel which regulates the passage of ions like chloride, thiocyanate and helps in maintaining equilibrium of ions and water on both sides of the cell.Thus in Cystic fibrosis patients with defective CFTR gene the protein regulated channel is not formed and there will be no transport of ions into the cell. Chloride and thiocyanate are trapped outside the cells in the skin and outside the airway in the lungs. The salt concentration in the sweat is elevated and there is loss of much sweat in cystic fibrosis individuals compared to normal individuals which forms the basis for ‘sweat test’ – one of the diagnostic tests of Cystic fibrosis.

In the lungs and pancreas, viscosity of the mucus is increased which leads to obstruction. Obstruction sets the stage for chronic infection, inflammation and epithelial damage in the lungs. Damage in the pancreas is due to accumulation of digestive enzymes and damage to intestines is due to thick faeces that blocks the passage. Death results typically from Obstructive airway disease at an average age of 40 years.

Symptoms of Cystic fibrosis and Systems affected:

The systems and organs affected in the body of Cystic fibrosis patient are

1. Lungs and Sinuses

2. Pancreas

3. Liver

4. Gallbladder

5. Gastrointestinal system

6. Endocrine system

7. Reproductive system

The symptoms are based on the system or organ affected and are as follows:

Lungs and Sinuses if affected result in:

a. Chronic lung infections – Fever, Cough, Fatigue

b. Breathlessness

c. wheezing

d. Nasal congestion due to Nasal Polyps

d. Hemoptysis in complicated cases.

e. Pneumothorax and finally respiratory failure.

Pancreas if affected:

a. Reduced absorption of fat soluble vitamins and lipids.

b. Recurrent bouts of Pancreatitis.

c. Steatorrhea – Presence of excess of excess fat in the stools due to fat malabsorption results in pale coloured foul smelling stools

d. Diabetes.

Liver and gallbladder if affected:

a. Blocks biliary ducts

b. Cirrhosis

c. Gallstones

Gastrointestinal system if affected:

a. Distal intestinal obstruction results in Bloating due to gas

b. Constipation – Pain abdomen

c. Meconium ileus

d. Intussusception

e. Colonic strictures

f. Malnutrition

g. Hypoproteinemia

h. Nausea and vomiting

i. Loss of weight

Endocrine System if affected:

a. Type 1 and Type 2 Diabetes due to damaged Pancreas

b. Osteoporosis – Weakened bones due to Vitamin D malabsorption

c. Clubbing of fingers

Reproductive System:

a. Male Infertility

b. Azoospermia – Reduction in sperm count

c. CBAVD – Congenital absence of vas deferens – Seen in almost all patients.

d. Moderate reduction of Fertility in Females.

Early diagnosis and prompt treatment with modification of lifestyle should be aimed at as there is no prevention of the disease.