Alpha-1-antitrypsin deficiency is a condition caused by an abnormality in the gene for a protease inhibitor called alpha-1-antitrypsin.
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.
Two main organs are affected by alpha-1-antitrypsin deficiency, the liver and the lungs. It leads to:
- Liver cirrhosis after 50 years old
- Bronchiectasis and emphysema in the lungs after 30 years old
In The Liver
Normally, alpha-1-antitrypsin is created in the liver. In alpha-1-antitrypsin deficiency, an abnormal “mutant” version of this protein is produced, rather than the normal alpha-1-antitrypsin protein. This mutant protein gets trapped in the liver, builds up, and causes liver damage. This liver damage progresses to cirrhosis over time. It can lead to hepatocellular carcinoma.
In The Lung
The lack of a normal, functioning alpha-1-antitrypsin protein leads to an excess of protease enzymes that attack the connective tissue in the lungs. This leads to bronchiectasis and emphysema over time.
- 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
- 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)
Last updated November 2020