Test Catalog

Test Id : A1ALC

Alpha-1-Antitrypsin Proteotype S/Z, LC-MS/MS, Serum

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

Identification of homozygous and heterozygous S and Z proteotypes of alpha-1-antitrypsin deficiency

Profile Information
A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.

Test Id Reporting Name Available Separately Always Performed
A1ASZ A1AT Proteotype S/Z, LC-MS/MS No Yes
AATP Alpha-1-Antitrypsin, S Yes, (order AAT) Yes

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
A1APR Alpha-1-Antitrypsin Phenotype, S Yes, (order A1APP) No

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

If the mass spectrometry proteotype and quantitative serum level are discordant, then phenotyping will be added and performed at an additional charge.

 

See Alpha-1-Antitrypsin-A Comprehensive Testing Algorithm

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

Method Name
A short description of the method used to perform the test

A1ASZ: Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

AATP: Nephelometry

A1APR: Isoelectric Focusing

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

A1AT Proteotype S/Z, LC-MS/MS, S

Aliases
Lists additional common names for a test, as an aid in searching

a-1-Antitrypsin, Proteotype

A1A Proteotyping

AAT Proteotyping

Alpha 1 Antitrypsin

Alpha-1-Antitrypsin by MS

Anti-Alpha-1-Trypsin

Antitrypsin

Antitrypsin, Proteotyping

Pi Typing (Alpha-1-Antitrypsin Proteotyping)

Protease Inhibitor Allo Typing

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

If the mass spectrometry proteotype and quantitative serum level are discordant, then phenotyping will be added and performed at an additional charge.

 

See Alpha-1-Antitrypsin-A Comprehensive Testing Algorithm

Specimen Type
Describes the specimen type validated for testing

Serum

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 1.25 mL

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

Forms

If not ordering electronically, complete, print, and send a Gastroenterology and Hepatology Client Test Request (T728) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.5 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis OK
Gross lipemia Reject
Gross icterus OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 28 days
Ambient 28 days
Frozen 28 days

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

Identification of homozygous and heterozygous S and Z proteotypes of alpha-1-antitrypsin deficiency

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

If the mass spectrometry proteotype and quantitative serum level are discordant, then phenotyping will be added and performed at an additional charge.

 

See Alpha-1-Antitrypsin-A Comprehensive Testing Algorithm

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 1129 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 those of Northern European ancestry. The diagnosis of A1A deficiency is initially made by quantitation of protein levels in serum followed by determination of specific allelic variants by isoelectric focusing (IEF). 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 variant 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 has been the primary method for characterizing variants, although 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. A proteomic method using trypsin-digested sera can detect the mutated peptides of the S and Z alleles but can miss disease alleles other than the S and Z alleles. This test combines all of these methods to provide a comprehensive result.

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.

ALPHA-1-ANTITRYPSIN:

100-190 mg/dL

 

ALPHA-1-ANTITRYPSIN PROTEOTYPE:

Negative for S and Z phenotype (Non S Non Z)

Interpretation
Provides information to assist in interpretation of the test results

For each of the possible alpha-1-antitrypsin (A1A) genotypes there is an expected range for the total serum level of A1A. However, a number of factors can influence either the A1A serum level or the A1A proteotype results, including acute illness (A1A is an acute-phase reactant), protein replacement therapy, the presence of other rare variants, or the presence of rare DNA alterations (ie, polymorphisms). When the serum level differs from what is expected for that proteotype (ie, discordant), additional studies are performed to ensure the most appropriate interpretation of test results. Additional follow-up may include A1A phenotyping by isoelectric focusing, obtaining additional clinical information, and DNA sequencing. See Alpha-1-Antitrypsin Testing Result Table.

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

This assay will not detect 5% of the known genetic variants that cause alpha-1-antitrypsin (A1A) deficiency. Therefore, the absence of a detectable genetic variant does not rule out the possibility that an individual is a carrier of, or affected with, this disease.

 

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 variants 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.

 

Errors in interpretation may occur if patients have had a recent blood transfusion or are on A1A replacement therapy.

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

1. Stoller JK, Aboussouan LS: Alpha-1-antitrypsin deficiency. Lancet. 2005 Jun 25-Jul 1;365(9478):2225-2236

2. 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 Feb;111(2):394-403

3. Murray JD, Willrich MA, Krowka et al: Liquid chromatography-tandem mass spectrometry based alpha1-antitypsin (AAT) testing, Am J Clin Clin Pathol. 2021 Mar 15;155(4):547-552

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

Method Description
Describes how the test is performed and provides a method-specific reference

Alpha-1-Antitrypsin Proteotype S/Z:

Proteins from patient sera are denatured, reduced, and digested with trypsin to form peptides. Labeled internal standards are added to the peptide mixture and subjected to selective reaction monitoring (SRM) liquid chromatograph-tandem mass spectrometry analysis. The presence or absence of the S and Z mutated peptides are determined by SRM peptide-specific m/z values for both the mutated and nonmutated peptides.(Chen Y, Snyder MR, Zhu Yi, et al: Simultaneous phenotyping and quantification of alpha-1-antitrypsin by liquid chromatography-tandem mass spectrometry. Clin Chem. 2011 Aug;57[8]:1161-1168)

 

Alpha-1-Antitrypsin:

In this Siemens Nephelometer II method, the light scattered onto the antigen-antibody complexes is measured. The intensity of the measured scattered light is proportional to the amount of antigen-antibody complexes in the sample under certain conditions. If the antibody volume is kept constant, the signal behaves proportionally to the antigen volume.

 

A reference curve is generated by a standard with a known antigen content on which the scattered light signals of the samples can be evaluated and calculated as an antigen concentration. Antigen-antibody complexes are formed when a sample containing antigen and the corresponding antiserum are put into a cuvette. A light beam is generated with a light emitting diode (LED), which is transmitted through the cuvette. The light is scattered onto the immuno-complexes that are present. Antigen and antibody are mixed in the initial measurement, but no complex is formed yet. An antigen-antibody complex is formed in the final measurement.

 

The result is calculated by subtracting value of the final measurement from the initial measurement. The distribution of intensity of the scattered light depends on the ratio of the particle size of the antigen-antibody complexes to the radiated wavelength.(Instruction manual: Siemens Nephelometer II. Siemens, Inc; Version 2.3, 2008; Addendum to the Instruction Manual 2.3, 08/2017)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday, Thursday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

7 to 14 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

14 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

82103-Alpha-1-antitrypsin

82542-A1AT proteotype S/Z, LC-MS/MS

82104-Alpha-1-antitrypsin phenotype (if appropriate)

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
A1ALC A1AT Proteotype S/Z, LC-MS/MS, S In Process
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
AATP Alpha-1-Antitrypsin, S 6771-0
34855 A1AT Proteotype S/Z, LC-MS/MS 49244-7

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports