Test Catalog

Test ID: SERPZ    
SERPINA1 Gene, Full Gene Analysis, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Identification of causative mutations when a deficient serum level of alpha-1-antitrypsin is not explained by routine testing, such as proteotyping, genotyping, or isoelectric focusing phenotyping.


Determining the specific allelic variant (full gene analysis) for prognosis and genetic counseling

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Alpha-1-antitrypsin (A1A) is a protein that inhibits the enzyme neutrophil elastase. It is predominantly synthesized in the liver and secreted into the bloodstream. The inhibition function is especially important in the lungs because it protects against excess tissue degradation. Tissue degradation due to A1A deficiency is associated with an increased risk for early onset panlobular emphysema, which initially affects the lung bases (as opposed to smoking-related emphysema, which presents with upper lung field emphysema). Patients may become symptomatic in their 30s and 40s. The most frequent symptoms reported in a National Institute of Health study of 1,129 patients with severe deficiency (mean age 46 years) included cough (42%), wheezing (65%), and dyspnea with exertion (84%). Many patients were misdiagnosed as having asthma. It is estimated that approximately one-sixth of all lung transplants are for A1A deficiency.


Liver disease can also occur, particularly in children; it occurs much less commonly than emphysema in adults.


A1A deficiency is a relatively common disorder in Northern European Caucasians. The diagnosis of A1A deficiency is initially made by quantitation of protein levels in serum followed by phenotyping-determination of specific allelic variants by isoelectric focusing (IEF), genotyping-DNA based detection of specific mutations, or proteotyping-using liquid chromatography-tandem mass spectrometry (LC-MS/MS). While there are many different alleles in this gene, only 3 are common. The 3 major alleles include: M (full functioning, normal allele), S (associated with reduced levels of protein), and Z (disease-causing mutation associated with liver disease and premature emphysema). The S and Z alleles account for the majority of the abnormal alleles detected in affected patients. As a codominant disorder, both alleles are expressed. An individual of SZ or S- null genotype may have a small increased risk for emphysema (but not liver disease) due to slightly reduced protein levels. On the other hand, an individual with the ZZ genotype is at greater risk for early onset liver disease and premature emphysema.


Smoking appears to hasten development of emphysema by 10 to 15 years. These individuals should be monitored closely for lung and liver function.


Historically, IEF phenotyping has been the primary method for characterizing variants, though in some cases the interpretation is difficult and prone to error. Serum quantitation is helpful in establishing a diagnosis but can be influenced by other factors. IEF phenotyping, LC-MS/MS proteotyping, and DNA-based genotyping are routinely used to test for deficiency alleles, but can miss disease alleles other than the S and Z alleles. In patients suspected to have alpha-1 antitrypsin deficiency based on clinical findings or serum alpha-1-antitrypsin (AAT) levels, who do not have evidence of the SZ or ZZ genotype by routine methods, this gene analysis assay may provide useful information. Full sequencing of the SERPINA1 coding region is performed for the detection of rare non-S or non-Z disease mutations.


See Alpha-1-Antitrypsin-A Comprehensive Testing Algorithm in Special Instructions.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.


Interpretation Provides information to assist in interpretation of the test results

All detected alterations are evaluated according to American College of Medical Genetics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

A small percentage of individuals who are carriers or have a diagnosis of alpha-1 antitrypsin deficiency may have a mutation that is not identified by this method (eg, large genomic deletions, promoter mutations). The absence of a mutation, therefore, does not eliminate the possibility of positive carrier status or the diagnosis of alpha-1 antitrypsin deficiency. For testing of at risk family members, it is important to first document the presence of a SERPINA1 gene mutation in an affected family member.


In some cases, DNA alterations of undetermined significance may be identified.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in the interpretation of results may occur if information given is inaccurate or incomplete.


Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424

2. Stoller JK, Aboussouan LS: Alpha-1-antitrypsin deficiency. Lancet 2005;365:2225-2236

3. McElvaney NG, Stoller JK, Buist AS, et al: Baseline characteristics of enrollees in the National Heart, Lung and Blood Institute Registry of alpha 1-antitrypsin deficiency. Alpha 1-Antitrypsin Deficiency Registry Study Group. Chest 1997;111:394-403

4. Snyder MR, Katzmann JA, Butz ML, et al: Diagnosis of alpha-1-antitrypsin deficiency: an algorithm of quantification, genotyping, and phenotyping. Clin Chem 2006;52:2236-2242

5. Graham RP, Dina MA, Howe SC, et al: SERPINA1 full-gene sequencing identifies rare mutations not detected in targeted mutation analysis. J Mol Diag 2015;17:689-694

Special Instructions Library of PDFs including pertinent information and forms related to the test