Alpha-1 Antitrypsin Deficiency

Question 1

Alpha-1-antitrypsin deficiency

Answer 1

Alpha-1-antitrypsin deficiency is a condition caused by an abnormality in the gene for a protease inhibitor called alpha-1-antitrypsin.

Question 2

Pathogenesis of A1-AT

Answer 2

Elastase is an enzyme secreted by neutrophils. This enzyme digests connective tissues. Alpha-1-antitrypsin (A1AT) is mainly produced in the liver, travels around the body and offers protection by inhibiting the neutrophil elastase enzyme. A1AT is coded for on chromosome 14. In A1AT deficiency, there is an autosomal recessive defect in the gene for A1AT.

Question 3

What organs are affected in A1AT?

Answer 3

Liver cirrhosis after 50 years old - can proceed to hepatocellular carcinoma.
Bronchiectasis and emphysema in the lungs after 30 years old.

Question 4

Diagnosis of A1AT

Answer 4

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 5

Management of A1AT

Answer 5

Stop smoking (smoking dramatically accelerates emphysema)
Symptomatic management
NICE recommend against the use of replacement alpha-1-antitrypsin, however the research and debate is ongoing regarding the possible benefits
Organ transplant for end-stage liver or lung disease
Monitoring for complications (e.g. hepatocellular carcinoma)