Alpha-1-Antitrypsin Deficiency
Alpha-1-Antitrypsin (AAT) Deficiency is a common genetic disorder predisposing to respiratory and hepatic disease. AAT Deficiency has co-dominant inheritance and alleles are named with a protease inhibitor or “PI” type.
PrintAlpha-1-Antitrypsin (AAT) Deficiency is a common genetic disorder predisposing to respiratory and hepatic disease. AAT Deficiency has co-dominant inheritance and alleles are named with a protease inhibitor or “PI” type.
More than 100 variants in the AAT gene have been described, with rare variants causing approximately 5% of deficiency cases. This Ambry Test is a Gene Sequence Analysis with a detection rate of approximately 99%.
Routine serum protein measurement and phenotyping are adequate for testing symptomatic individuals and those at increased risk in most cases. The Ambry Test is a valuable adjunct to those biochemical tests and is appropriate for:
- Resolving discrepancies and ambiguities between clinical presentation, protein measurement, and/or phenotyping.
- Carrier Testing for relatives of patients with known mutations.
Alpha-1-Antitrypsin (AAT) Deficiency is a common genetic disorder predisposing to respiratory and hepatic disease. AAT Deficiency has codominant inheritance, with each allele contributing individually to the patient’s phenotype. Alleles are named with a protease inhibitor or “PI” type. Patients with the most common severe form of the disease (homozygous Z alleles, or PI*Z/PI*Z) are at increased risk of neonatal cholestasis; juvenile or adult cirrhosis, sometimes requiring liver transplant; and chronic obstructive pulmonary disease including early-onset emphysema. Less frequent complications include hepatocellular carcinoma, panniculitis, and vasculitis. The less severe S allele causes reduced serum levels of AAT. Null alleles produce little or no protein. Either the S or a null allele may cause symptoms when present in combination with another severe deficiency allele.
While not all patients with AAT Deficiency will have clinically significant symptoms, the condition is considered widely under-recognized.1,2 Over 300,000 people in the U.S. and Canada are estimated to have PI SZ or PI ZZ phenotypes.3 In these countries, approximately 1/44 people are carriers of the Z allele and 1/17 carry the S allele.3 AAT Deficiency affects all racial subgroups.3
More than 100 variants in the AAT gene have been described, with over one third of those known to cause abnormal protein expression.2 Rare genetic variants are collectively not so rare, causing approximately 5% of deficiency cases.1
The American Thoracic Society and the European Respiratory Society have published guidelines for AAT testing in symptomatic individuals and those at increased risk due to family history or environmental exposures.2
Routine serum protein measurement of AAT and PI type testing of serum with polyacrylamide isoelectric focusing (PIEF) are adequate for diagnosis in most cases.
The Ambry Test: Alpha-1-Antitrypsin Deficiency is a valuable adjunct to these biochemical tests and is appropriate for:
- resolving discrepancies and ambiguities between clinical presentation, protein measurement, and/or phenotyping
- carrier testing for relatives of patients with known mutations
Please see our Gene Report: The Role of Full Gene Sequence Analysis in the Diagnosis of Alpha-1-Antitrypsin Deficiency for a more detailed discussion of situations that can complicate or prevent a correct biochemical diagnosis. The Ambry Test: Alpha-1-Antitrypsin Deficiency, as a complete molecular analysis, can resolve the patient’s diagnosis at the DNA level.
The Ambry Test: Alpha-1-Antitrypsin Deficiency is a full gene analysis performed by PCR-based double-stranded automated sequencing in the sense and antisense directions for exons 2 through 5 of the SERPINA1 gene, plus at least 20 base pairs into the the 5’ and 3’ ends of all introns. Specific mutation analysis for known family mutations in SERPINA1 is also available.
The Ambry Test: Alpha- 1-Antritryspin Deficiency clinical mutation detection rate is approximately 99%.
Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (1st choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Saliva: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Send 20 μg in TE at 50-100 ng/μl. Store frozen and ship on ice or dry ice.
Prenatal: Prenatal testing is available. Please call an Ambry Genetic Counselor to discuss your case.
Blood spots not accepted for this test.
| Test Code | Technique | CPT Codes |
|---|---|---|
| 1140 | SERPINA1 Gene Sequence Analysis | 83891x1, 83894x5, 83898x4, 83904x10, 83909x10, 83912x1 |
| Technique | Days |
|---|---|
| SERPINA1 Gene Sequence Analysis | 10-21 |
1World Health Organization. Bulletin of the WHO. 1997;75:397-415 .
2American Thoracic Society and European Respiratory Society. Am J Respir Crit Care Med. 2003;168:818-900.
3deSerres FJ. Chest. 2002;122:1818-1829