Common Non Cancerous Genetic Disorders

Question 1

What is the kind of inheritance of Cystic Fibrosis?

Answer 1

Autosomal Recessive Inheritance

Question 2

What are the consequences of Cystic Fibrosis?

Answer 2

• Recurrent lung infections
• Bronchiectasis
• Obstructive Lung Disease

Question 3

What is the gene responsible for Cystic Fibrosis?

Answer 3

• There are more than 1000 different mutations in the CFTR gene
• 70% : deletion of Phenylalanine at position 508 d-F508 - more severe
• Mutation of R117H : arginine at 117 is substituted with histidine (milder)

Question 4

What is the pathology involved in d-F508 mutation?

Answer 4

Normal folding of protein is prevented – degraded by proteosome – chloride ion channel cannot be inserted into plasma membrane

Question 5

What is the pathology involved in R117H mutation?

Answer 5

The chloride ion channels respond poorly to cAMP – do not remain open as long as they should – less pancreatic insufficiency

Question 6

What is the function of normal chloride ion channel in an airway?

Answer 6

Efflux of Chloride ions – Water leaves the cells to the surface of the airway lumen – dilution of secretion

Question 7

What are the common sites affected in a patient with cystic fibrosis?

Answer 7

Lungs, pancreas and vas deferens

Question 8

What is the main reason of recurrent lung infection of a patient with cystic fibrosis?

Answer 8

Failure of water to leave the cells to dilute the airway lumen secretion – thick secretions – clogging up the tubes – secretions become culture medium for bacteria

Question 9

What bacterial infection is common in the lungs of a patient with Cystic Fibrosis and how is this infection commonly treated?

Answer 9

Pseudomonas aeruginosa infection. Treat with aminoglycoside such as amikacin, tobramycin or quinolones such as ciprofloxacin.

Question 10

What are the clinical features of Cystic Fibrosis?

Answer 10

1. Lungs
   - bronchiectasis in childhood : initially upper lobe –> progresses to other lobes
   - respiratory failure : progressive lung damage
   - pneumothorax
   - haemoptysis
   - cor pulmonale : scarred lung causes pulmonary hypertension
2. GIT
   - exocrine pancrease insufficiency
   - intestinal obstruction
   - biliary cirrhosis
   - portal hypertension
3. Male infertility
   - congenital bilateral absence of vas deferens

Question 11

Management of Cystic Fibrosis?

Answer 11

Antibiotic
Oxygenation
Oral Pancreatic Enzyme Capsules

Question 12

Diagnosis of Cystic Fibrosis?

Answer 12

Newborn screening : Immunoreactive Trypsin Levels

• Confirmatory test : DNA test –> Oligonucleotide Ligation Assay
• Sweat test : increases Chloride ions (sweat glands fail to reabsorb the amount of chloride ions back into the body)

Question 13

What is Cascade Screening?

Answer 13

Testing of primary relatives of an individual with an identified mutation with the help of the patient