There are 2 tests required to diagnose alpha-1 antitrypsin deficiency. The first test is an alpha-1 antitrypsin (AAT) level, the second more informative test is an AAT phenotype. An AAT phenotype is the definitive test for AAT deficiency as it precisely identifies the type of AAT protein present in the blood, for example Z or S. Ordering an AAT level will measure how much of this protein is in the blood and is a useful screening tool, for example in the setting of COPD. However, this test does not provide a definitive diagnosis. This is because AAT is an acute phase protein (like CRP) and can be elevated during infection and inflammation. If you have a strong suspicion of AAT deficiency in your patient, or if there is a family history of AAT deficiency, order both AAT level and AAT phenotype.
For more information on testing see “Pitfalls and caveats in α1-antitrypsin deficiency testing: a guide for clinicians” published in the Lancet Respiratory Medicine in 2019.
Who Should be Tested?The World Health Organisation (WHO), American Thoracic Society (ATS), and European Respiratory Society (ERS) together recommend the following cohorts for screening;
- COPD, regardless of age or smoking history
- Severe, non-responsive/refractory asthma
- Cryptogenic liver disease
- All first-degree relatives of people with diagnosed AAT deficiency
- Individuals with reduced serum levels of AAT