Alpha-1-Antitrypsin Deficiency Profile

CPT CODE:

USEFUL FOR:

This is Mayo's preferred approach for diagnosing A1A deficiency (A1A quantitation and genotype)
Determining the specific allelic variant (genotyping) for prognosis and genetic counseling

SPECIMEN REQUIRED:

Blood and serum are required for this test.
"Molecular Genetics - Congenital Inherited Diseases Patient Information Sheet" (Supply T521 or see Special Instructions) is required for all orders. If not orderingelectronically, please submit the above information sheetalong with a "Molecular Genetics Request Form" (Supply T245)with the specimen. An "Informed Consent for DNA Testing"(Supply T576) is available. See Special Instructions for acopy of the form.
Specimen must arrive within 96 hours of draw.
BloodDraw blood in a lavender-top (EDTA) tube or a yellow-top (ACD) tube, and send 3 mL of EDTA or ACD whole blood in original VACUTAINER. Invert several times to mix blood.  Forward unprocessed whole blood promptly at ambient temperature. Note: Label specimen appropriately (blood).
SerumDraw blood in a plain, red-top tube(s) or a serum gel tube.Spin down and send 1 mL of serum refrigerated.Note: Label specimen appropriately (serum).

TRANSPORT TEMPERATURE:

VariesAmbient\Refrig OK\Frozen NO - bloodRefrig\Frozen OK\Ambient NO - serum

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 to protect against excess tissue degradation. Tissue degradation due to A1A deficiency is associated with an increased risk for early onset panlobar 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 30's and 40's. The most frequent symptoms reported in a National Institute of Health (NIH) 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 determining 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), with S and Z accounting for the majority of the abnormal alleles detected in affected patients. As a codominant disorder, both alleles are expressed. An individual of SZ or Snull 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. However, in some cases the interpretation of IEF is difficult and prone to error. DNA-based assays are now available for the characterization of deficiency alleles in patients with A1A deficiency.  See "Alpha-1-Antitrypsin - A Comprehensive Testing Algorithm" in Special Instruc

CLINICAL INTERPRETATION:

For each of the possible 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 genotype results, including acute illness (A1A is an acute phase reactant), protein replacement therapy, the presence of other rare variants and/or the presence of DNA polymorphisms. When the serum level differsfrom what is expected for that genotype (ie, discordant), additional studies are performed to ensure the most appropriate interpretation of test results. Additional follow-up may include A1A phenotyping by IEF, obtaining additional clinical information, and DNA sequencing.See "Alpha-1-Antitrypsin Reflex Table" in Special Instructions.
The report will include specimen information, pedigree (when appropriate), assay information, background information, and estimate of carrier risk based on test results. The report will alsoinclude quantitative levels of A1A enzyme. A1A phenotype will be included when necessary.
Normal individuals will have "non-Z, non-S" genotypes.

REFERENCE VALUES:

ALPHA-1-ANTITRYPSIN GENOTYPING

      An interpretive report will be provided.

ALPHA-1-ANTITRYPSIN

      100-190 mg/dL