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Test ID: A1ALC Alpha-1-Antitrypsin Proteotype S/Z by LC-MS/MS, Serum

Useful For

Determining the specific proteotype for prognosis and genetic counseling for patients with alpha-1-antitrypsin deficiency

Profile Information

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

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

Testing Algorithm

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 in Special Instructions.

Reporting Name

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

Specimen Type

Serum


Specimen Required


Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 1.25 mL


Specimen Minimum Volume

0.5 mL

Specimen Stability Information

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

Clinical Information

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 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 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 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. 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

ALPHA-1-ANTITRYPSIN

100-190 mg/dL

 

ALPHA-1-ANTITRYPSIN PROTEOTYPE

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

Interpretation

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 DNA 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 in Special Instructions.

Clinical Reference

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

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;111:394-403

Day(s) and Time(s) Performed

Monday, Thursday; 10 a.m.

Analytic Time

7 days

CPT Code Information

82103-Alpha-1-antitrypsin

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

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

LOINC Code Information

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
AATP Alpha-1-Antitrypsin, S 6771-0
34855 A1AT Proteotype S/Z, LC-MS/MS 49244-7

Method Name

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

AATP: Nephelometry

A1APR: Isoelectric Focusing

Test Classification

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 U.S. Food and Drug Administration.

Forms

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

Mayo Clinic Laboratories | Gastroenterology Catalog Additional Information:

mml-gi-liver-genetic