A1AT deficiency

Question 1

What are the genetic changes in A1AT deficiency?

Answer 1

Autosomal recessive
Mutation of protease inhibitor gene (also called serpina-1 gene) on chromosome 14

Question 2

What does A1AT stand for?

Answer 2

Alpha 1 antitrypsin

Question 3

What does A1AT normally do?

Answer 3

Normally inhibits neutrophil elastase (NE, which degrades elastic tissue)

Question 4

Where is is A1AT made?

Answer 4

Liver
(so when fibrosis or cirrhosis, even worse at producing A1AT, vicious cycle)

Question 5

What are the 2 majorly affected organs from A1AT deficiency?

Answer 5

Lungs
Liver

Question 6

How are the lungs affected by A1AT?

Answer 6

Deficient A1AT means high levels of NE (neutrophil elastase) so elastic tissue is degraded causing alveolar duct collapse.
Air is trapped and is characteristic panacinar emphysema

Question 7

How is the liver affected by A1AT?

Answer 7

Deficient A1AT means high NE (neutrophilic elastase). This causes the liver to be unprotected and soon becomes fibrotic. Progresses to cirrhosis and increases risk of HCC

Question 8

Describe a typical person to present with A1AT deficiency

Answer 8

Young/ middle aged male
Little to no smoking
COPD-like symptoms

Question 9

What are symptoms of A1AT deficiency?

Answer 9

Dyspnoea
Chronic cough
Sputum production
Barrel chest
May be jaundiced or have other liver symptoms

Question 10

How is A1AT deficiency diagnosed?

Answer 10

Very low serum A1AT (under 20 mmol/l)

Barrel chest on exam (chest XR shows hyperinflated lungs)

CT: panacinar emphysema

Spirometry shows obstruction (FEV1:FVC is <0.7)

Genetic testing: positive PI (protease inhibitor gene) mutation

Question 11

What is treatment for A1AT?

Answer 11

No treatment

Stop smoking (if smoke)

Manage emphysema eg inhalers

Consider hepatic decompensation patients for liver transplant