Alpha 1 Antitrypsin Type S/Z (Sendout)

Useful For: Identification of homozygous and heterozygous S and Z proteotypes of alpha-1-antitrypsin deficiency. If the mass spectrometry proteotype and quantitative serum level are discordant, then phenotyping will be added and performed at an additional charge.

Ordering Recommendation:

• Initial Testing:
  • Recommended First Step: perform Alpha 1 Antitrypsin [A1AT].
  • Include CRP, high sensitivity [HSCRP] to check for an acute phase response.
    • Note: An acute phase response can elevate a genetically low A1AT, potentially confounding results.
• If CRP is High:
  • If CRP is high and the A1AT is low, wait for inflammation to resolve before measuring again.
• If A1AT is Low with Non-elevated (i.e. normal) CRP:
  • Proceed to classify the decrease with Mayo proteotype test (mass spectrometry, this test).
    • Mayo Alpha-1-Antitrypsin Comprehensive Testing Algorithm
    • This test will determine if the decrease is due to a common mutation (Z/S).
  • If the mass spectrometry proteotype assay is inconclusive, phenotyping (isoelectric focusing, Alpha 1 Antitrypsin Phenotype (Sendout) [RA1AP]) will be performed reflexively.
• Last Resort:
  • Consider full SERPINA1 gene sequencing for unusual cases (to order sequencing, contact the Laboratory Medicine Resident via the paging operator at 206-598-6190).

Reference Values:

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 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:

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.

Outside Laboratories: Centrifuge sample and transfer serum to a separate plastic vial. Refrigerate serum.

Stability: Refrigerated (preferred): 28 days; Frozen: 28 days; Ambient: 28 days.

Reject Due To: Gross lipemia. Gross hemolysis and gross icterus are acceptable.

Centrifuge sample and transfer serum to a separate plastic vial. Refrigerate serum.

Sendouts:

• Order Mayo Test: A1ALC.
• Interfaced: Yes.

Stability: Refrigerated (preferred): 28 days; Frozen: 28 days; Ambient: 28 days.

Reject Due To: Gross lipemia. Gross hemolysis and gross icterus are acceptable.