This information is an aid to the diagnosis and management of patients and their relatives with alpha-1 antitrypsin deficiency.
How does AATD occur?
There are many different genetic variants of AAT.
M is the normal variant. The two most important abnormal variants are called S and Z. S produces moderately low levels of AAT whilst Z produces very little AAT.
There are varying degrees of severity depending on the combination of genes
- 90% of North Europeans are MM and have normal AAT levels.
- MZ or MS (carriers) and SS have lower, but sufficient levels of AAT. They do not have a significant increased risk of lung or liver disease, but should be advised that is sensible not to smoke, and to take alcohol in moderation.
- SZ individuals have AATD. They have a 60% risk of developing early onset COPD, and an increased risk of liver disease.
- ZZ individuals have AATD. All will develop early onset COPD, and have increased risk of liver disease.
Who to test
- People with clinical features suggestive of AATD (please give clinical details on sample referral form).
- Siblings of an affected person. Testing of other healthy relatives is not generally recommended.
- AATD is an adult onset condition therefore carrier testing is not recommend in healthy children. To clarify the risk to children partners of an affected or carrier person may be tested
- If testing is declined by patient – give lifestyle advice regarding smoking and alcohol.
How to test
- 2 to 4ml blood in EDTA (anticoagulant) tube sent with DNA request card to Northern Molecular Genetic Service via your local hospital pathology department.
- Include reasons for testing or name of affected relative on sample referral form where applicable.
- For patients with clinical features, you should also send serum AAT level (clotted blood sample to Biochemistry).
By completing the form, this indicates that patients have consented to testing, and DNA being stored by the testing laboratory.
Results
Results are usually available within 4 weeks and will be returned to refer given on the request.
Interpretation of genetic results and further actions
| Test result | Interpretation and management |
|---|---|
| MM | Normal. No further AATD management required. |
| MZ | Carrier (partial AATD) Unlikely to impact on health. Smoking and alcohol advice as per general population. If a couple of childbearing ages are both MZ carriers, referral to genetics can be considered. |
| MS | Carrier (partial AATD) Unlikely to impact on health. Smoking and alcohol advice as per general population. |
| SS | Partial deficiency Unlikely to impact on health. Smoking and alcohol advice as per general population. |
| ZZ | Affected Significantly increased risk of COPD and increased risk of liver disease. Encourage reporting symptoms which may suggest COPD and/or chest infection early as prompt treatment reduces lung tissue damage. Smoking cessation and alcohol moderation advice. Referral on to appropriate specialties (respiratory or liver teams) in symptomatic individuals. |
| SZ | Affected Increased risk of COPD (but lower than in ZZ individuals) Risk of liver disease is not thought to be increased. Management advice as per ZZ for COPD risk |
| Other results (rare) | See advice from laboratory |
