Alpha-1 antitrypsin deficiency

Question 1

Pathophysiology?

Answer 1

This is a common inherited condition caused by a lack of a protease inhibitor (alpha-1 antitrypsin) normally produced by the liver.

Question 2

What is the role of A1AT?

Answer 2

To protect cells from enzymes such as neutrophil elastase

Question 3

Where is this gene defect located?

Answer 3

Chromosome 14

Question 4

What is the inheritance pattern?

Answer 4

Autosomal recessive

Question 5

What does this condition classically cause?

Answer 5

Emphysema (i.e. COPD) in patients who are young and non-smokers

Question 6

Patients who manifest disease usually have which genotype?

Answer 6

PiZZ genotype

Question 7

What symptoms can occur?

Answer 7

• lungs: panacinar emphysema, most marked in lower lobes

- liver: cirrhosis and hepatocellular carcinoma in adults, cholestasis in children

Question 8

What investigations should be performed?

Answer 8

• A1AT concentrations

- spirometry

Question 9

What would be seen on spirometry?

Answer 9

Obstructive defects

Question 10

Management?

Answer 10

• no smoking
• supportive: bronchodilators, physiotherapy
• intravenous alpha1-antitrypsin protein concentrates
• surgery

Question 11

What surgery procedures can be performed?

Answer 11

• Lung volume reduction surgery

- Lung transplantation