Alpha-1-Antitrypsin deficiency

Question 1

What causes A1AD?

Answer 1

In A1AT deficiency, there is an autosomal recessive defect in the gene for A1AT.

Question 2

What pathology occurs in A1AD?

Answer 2

The liver and lungs are both affected

Liver:

• Cirrhosis (as mutant protein gets trapped and builds up in the liver causing damage)
• Can lead to HCC

Lungs:
- Causes bronchiectasis and emphysema in the lungs

Question 3

What does the A1AT protein usually do?

Answer 3

Inhibits neutrophil elastase enzyme which digests connective tissues.

So deficiency of this protein allows higher levels of elastase which attack connective tissue in the lung leading to emphysema and bronchiectasis.

Question 4

How does A1AD present?

Answer 4

COPD/emphysema in young patients and those who are non-smokers

Liver cirrhosis features e.g. jaundice, varices, splenomegaly etc…

Question 5

Investigations in suspected A1AD

Answer 5

Low serum-alpha 1-antitrypsin (screening test of choice)

Liver biopsy shows cirrhosis and acid-Schiff-positive staining globules (this stain highlights the mutant alpha-1-antitrypsin proteins) in hepatocytes

Genetic testing for the A1AT gene

High resolution CT thorax diagnoses bronchiectasis and emphysema

Question 6

Management of A1AD

Answer 6

Stop smoking

Supportive symptom management e.g. bronchodilators

Organ transplant for end-stage liver or lung disease

Monitoring for complications

(Intravenous alpha1-antitrypsin protein concentrates may be of benefit but NICE currently recommends against the use of this)