Alpha-1 antitrypsin deficiency (A1ATD)

Question 1

What is A1ATD?

Answer 1

Inherited disorder that affects the lungs and the liver due to an abnormality in the gene for a protease inhibitor called alpha-1-antitrypsin

Question 2

1) Elastase in an enzyme produced by what cell?
2) What does this enzyme do?
3) Where is alpha-1-antitrypsin produced?
4) What does alpha-1-antitrypsin do?

Answer 2

1) Neutrophils
2) Digests connective tissues
3) Liver (mainly)
4) Inhibits elastase

Question 3

1) What does A1ATD cause in the liver?
2) What does A1ATD cause in the lungs?
3) In A1ATD, what is the inheritance pattern that leads to a defect in the A1AT gene?
4) How does A1ATD cause damage to the liver?
5) How does A1ATD cause damage to the lungs?

Answer 3

1) Liver cirrhosis (after around 50 years)
2) Bronchiectasis and emphysema in the lungs (after around 30 years)
3) Autosomal recessive
4) Results in a buildup of the mutant protein in the liver which causes damage
5) Lack of a normal, functioning A1AT leads to an excess of protease enzymes that attack the connective tissue in the lungs

Question 4

1) What is the screening test of choice?
2) In this test, does a high value or a low value imply A1ATD?
3) What stain highlights the mutant alpha-1-antitrypsin proteins?
4) Name another investigation involved in the diagnosis of A1ATD

Answer 4

1) Serum-alpha 1-antitrypsin
2) Low
3) Periodic acid-Schiff (+ve)
4) High resolution CT thorax and genetic testing

Question 5

Name 2 aspects of the management of A1ATD

Answer 5

• Stop smoking
• Symptomatic management
• Treatment and prevention (vaccination) of any lung infections
• Monitoring for complications i.e. hepatocellular carcinoma