45_Genetic pulmonary disorders

Question 1

What are genetic pulmonary disorders?

Answer 1

Diseases that affect the lungs and are caused by genetic mutations or abnormalities in the DNA.

Question 2

How are genetic pulmonary disorders inherited?

Answer 2

They can be inherited from one or both parents or can occur spontaneously due to a new genetic mutation.

Question 3

What is cystic fibrosis?

Answer 3

It is an autosomal recessive disorder caused by a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Question 4

What is the most common mutation causing cystic fibrosis?

Answer 4

Delta F508 (Δ508).

Question 5

What happens in cystic fibrosis due to the mutation?

Answer 5

The mutation leads to defective chloride channels, causing mucus in various organs to become thick and sticky.

Question 6

What are the clinical features of cystic fibrosis?

Answer 6

Mucus impaction, recurrent or chronic productive cough and pulmonary infections, dyspnea, hemoptysis, clubbing of fingers, chronic obstructive lung disease with bronchiectasis, chronic sinusitis, pneumothorax, and cor pulmonale.

Question 7

What is the diagnosis process for CF?

Answer 7

Diagnosis is based on typical clinical features and sweat chloride test.

Question 8

What is the sweat chloride test?

Answer 8

It is a test indicated in all patients with suspected CF, where sweat is collected and the Cl- concentration is measured to confirm CFTR dysfunction.

Question 9

What is CFTR genetic testing?

Answer 9

It is a confirmatory test after an equivocal sweat test, which includes gene sequencing and deletion/duplication analysis to detect less common CFTR mutations.

Question 10

What are the treatments for CF?

Answer 10

Expectoration, treating colonization with antibiotics, bronchodilators, treating pulmonary complications, and pulmonary rehabilitation.

Question 11

What are some expectoration treatments for CF?

Answer 11

Physiotherapy, hypertonic saline, and pulmozyme.

Question 12

What antibiotics are used to treat colonization in CF?

Answer 12

Antibiotics that target therapy against H. influenzae, S. aureus, P. aeruginosa, and Stenotrophomonas maltophilia.

Question 13

What is the treatment for hemoptysis in CF?

Answer 13

Selective embolism of pulmonary artery.

Question 14

What is the treatment for PTX in CF?

Answer 14

Chest drainage.

Question 15

What is the purpose of nebulized beta-2 agonists in CF treatment?

Answer 15

To act as bronchodilators.

Question 16

What is Alpha-1 antitrypsin deficiency?

Answer 16

It is an inherited genetic disorder characterized by the accumulation of defective alpha-1 antitrypsin enzyme.

Question 17

What is the inheritance pattern of Alpha-1 antitrypsin deficiency?

Answer 17

Autosomal dominant (AD).

Question 18

What is the role of alpha-1 antitrypsin in the body?

Answer 18

It is a protease inhibitor that regulates enzymes such as elastase and trypsin, protecting cells from breakdown by neutrophil elastase.

Question 19

What happens when there is a gene mutation in alpha-1 antitrypsin?

Answer 19

It induces a conformational change in the structure of AAT protein, leading to dysfunctional AAT.

Question 20

What are the effects of Alpha-1 antitrypsin deficiency on the liver?

Answer 20

Accumulation of AAT in hepatocellular ER leads to hepatocyte destruction, hepatitis, and liver cirrhosis.

Question 21

What are the effects of Alpha-1 antitrypsin deficiency on the lungs?

Answer 21

Deficient AAT leads to uninhibited neutrophil elastase activity, causing destruction of the pulmonary parenchyma and panacinar emphysema.

Question 22

What are the clinical features of Alpha-1 antitrypsin deficiency?

Answer 22

Pulmonary symptoms include cough, wheezing, dyspnea, barrel chest, and diminished sounds. Hepatic symptoms include jaundice, hepatitis, cirrhosis, and increased risk of HCC.

Question 23

What are the diagnostic tests for Alpha-1 antitrypsin deficiency?

Answer 23

Serum tests show decreased antitrypsin protein levels and electrophoresis shows decreased alpha-1 peak. CXR shows low and flat diaphragm, widened intercostal spaces, and hyperinflation. Chest CT shows panacinar emphysema. Liver biopsy shows PAS positive, spherical inclusion bodies in hepatocytes.

Question 24

What is the treatment for Alpha-1 antitrypsin deficiency?

Answer 24

Avoid active and passive exposure to cigarette smoke, use symptomatic treatment such as bronchodilators, antitrypsin replacement in severe cases, and liver transplantation.

Question 25

In which patients should the diagnosis of Alpha-1 antitrypsin deficiency be considered?

Answer 25

In all patients with emphysema under the age of 50 years.

Question 26

What is Marfan syndrome?

Answer 26

An autosomal dominant connective tissue disorder that affects the microfibrils and elastin in connective tissue throughout the body.

Question 27

What are the systems associated with Marfan syndrome?

Answer 27

Cardiovascular system, musculoskeletal system, and the eyes.

Question 28

What is the etiology of Marfan syndrome?

Answer 28

Mutation of fibrillin-1 gene (FBN1) which leads to defective fibrillin, defective connective tissue microfibrils, and defective elastin.

Question 29

What are the clinical features of Marfan syndrome?

Answer 29

Hyperextensive skin, stretch marks, tall stature with long extremities, joint hypermobility, lens dislocation, severe myopia, mitral valve prolapse, aortic aneurysm, and aortic dissection.

Question 30

What are the diagnostic tests for Marfan syndrome?

Answer 30

Echocardiography for cardiovascular manifestations, slit-lamp examination to rule out lens abnormalities, and imaging tests such as skeletal X-rays and MRI.

Question 31

What is the treatment for aortic dilation in Marfan syndrome?

Answer 31

Beta blockers or aortic root replacement surgery.

Question 32

What is the treatment for lowering blood pressure in Marfan syndrome?

Answer 32

ARBs together with beta blockers.