Although Alpha-1 Antitrypsin Deficiency (AATD) is one of the most common genetic disorders in the world, it is often misdiagnosed. Many times patients are told they have asthma, bronchitis, symptoms related to stress, emphysema caused by smoking, or simply chronic obstructive pulmonary disease of unknown cause.
The most common indicators of AATD include shortness of breath, a chronic cough, and abnormal liver test results. If you have any of these symptoms there is a simple blood test that can detect Alpha-1 Antitrypsin (AAT) levels. This test is also recommended if you have relatives, especially siblings, who have been diagnosed with AATD, or if there is a family history of early emphysema, with or without smoking.
The laboratory test measures AAT levels in blood, which are usually reported within Australia using grams per litre (g/L), however alternative measures are milligrams per 100 ml (mg%) and micromoles per liter (µM/L). All measurements provide the same basic information on how much AAT is in the blood.
People with two healthy copies of the AAT gene produce the most AAT, and people with no copies of the gene at all produce the least. In addition, environmental factors can affect how much AAT is in the blood.
AAT levels can be affected by inflammation, trauma and malignancy. AAT levels may increase by up to 25% during inflammation. When discussing an AAT test with your physician, suggest that obtaining a marker for inflammation will be helpful in interpreting your result, eg. obtaining a measure of C-reactive protein (CRP). For more detailed information about CRP, see Pathology Tests Online > C-reactive protein.
An individual’s genetic makeup (genotype) combines with environmental factors to determine their phenotype. Here are the more common phenotypes and their corresponding blood alpha-1 levels.
|
Phenotype |
g/L | mg% | µM/L |
| MM (two normal copies) | 1.10 – 3.50 | 110 – 350 | 20.2 – 64.4 |
| MZ (one normal copy, one deficient copy) | 0.74 – 2.10 | 74 – 210 | 13.6 – 38.6 |
| SS (two marginally deficient copies) | 1.00 – 2.00 | 100 – 200 | 18.4 – 36.8 |
| SZ (one deficient copy, one marginally deficient copy) | 0.75 – 1.20 | 75 – 120 | 13.8 – 22.1 |
| ZZ (two deficient copies) | 0.20 – 0.45 | 20 – 45 | 3.68 – 8.28 |
| NULL (two nonfunctional copies) | 0 | 0 | 0 |
Table data source: American Thoracic Society / European Respiratory Society Statement: Standards for the Diagnosis and Management of Individuals with Alpha-1 Antitrypsin Deficiency > page 925 > Table 3, adjusted where test results are known for Australian patients.
AAT levels of 0.8 g/L (80 mg% or 14.7 µM/L) or less put you at greatest risk of developing AATD related emphysema. Smokers with intermediate deficiency levels (0.80 to 1.60 g/L) are also at increased risk of lung disease.
Of 13 testing laboratories around Australia, as at 3 December 2016 the published reference intervals for AAT levels had an average low of 0.94 g/L, and an average high of 1.98 g/L.
A couple of user-friendly online conversion calculators exist:
- UnitsLab.com
- Clinical Analyte Unit Conversion by Jay Clinical Services
In the table above, M refers to the normal gene. Over 75 combinations of gene variations (alleles) have been identified, some of which can cause AATD. The S, Z and Null genes are the most common ones that cause AATD. ZZ is the most common allele that causes lung disease.
The Null gene is one that produces no detectable levels of AAT. Alphas with the Null-Null phenotype are at the greatest risk of developing emphysema, yet none have suffered liver damage as a result of their AATD.
For more information on AAT testing, please see page numbered 5 of the AAA booklet. You may also find helpful:
- Information Sheet for Family Physicians
- Pathology Tests Explained > Alpha-1 Antitrypsin
- The Royal College of Pathologists of Australasia > Alpha-1 Antitrypsin