Alpha 1 Antitrypsin Deficiency

Question 1

Pathology

Answer 1

Alpha 1 antitrypsin deficiency is an inherited deficiency of a protease (elastase) inhibitor called alpha 1 antitrypsin.

This leads to an excess of protease enzymes that attack the liver and lung tissue and cause liver cirrhosis and lung disease.

Liver cirrhosis after 50 years old
Pulmonary basal emphysema after 30 years old

Question 2

Inheritance

Answer 2

Autosomal Recessive

Question 3

Diagnosis

Screening

Answer 3

Low serum alpha 1 antitrypsin. This is the screening test of choice.

Liver biopsy shows cirrhosis and acid-Schiff-positive staining globules (this is a test to stain the breakdown products of the action of the proteases) in hepatocytes

Genetic testing for the A1AT gene

High resolution CT thorax diagnoses pulmonary emphysema

Question 4

Management

Answer 4

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)