Testing for Alpha-1

Testing for Alpha-1 can be as simple as a finger stick

Testing for Alpha-1 Antitrypsin Deficiency (Alpha-1) can be as simple as a finger stick or as complex as sequencing an unusual strand of DNA. The setting and purpose of the testing determine the type of test needed. It is critical to remember that Alpha-1 is a laboratory diagnosis, not a clinical diagnosis. You can’t definitively make the diagnosis based on the patient’s medical history or physical examination. Diagnosis is made by a simple blood test.

Testing guidelines for different settings

The Alpha-1 Foundation has developed guidelines for the best testing practices in a variety of clinical settings. The guidelines are intended to help the medical community, individuals, and industry to understand how testing should be conducted, to ensure the most appropriate and efficient testing methods are used, and to protect patients rights and confidentiality.

See the complete Alpha-1 Foundation Testing Guidelines

Historically, early testing was performed using serum protein electrophoresis (SPEP). While widely available and easy to perform, this test is quite inaccurate compared with more specific tests currently available. However, if an SPEP is performed for other reasons and the results demonstrate an absent or decreased alpha1 band, further testing for the deficiency of alpha-1 antitrypsin (AAT) is definitely indicated.

The most widely available and least expensive specific test for Alpha-1 is the AAT serum level. This test, when performed correctly, can easily detect the most common forms of severe deficiency of AAT. There are problems with level testing however. First, level testing will not provide a definitive result in individuals who carry only a single abnormal AAT gene. In addition, there are some abnormal AAT genes that produce relatively normal levels of a defective protein and AAT level testing will miss these as well.

Finally, there is the issue of units of measurement. While some laboratories report their results in milligrams per deciliter (mg/dl) others report their results in micromoles (µM). In Europe, levels are often expressed as grams per liter (G/L). A number that represents a normal level in one unit of measurement could be significantly abnormal in a different unit. It is important to note both the units of measurement and the laboratory’s normal range when interpreting an AAT serum level (see table 1).

TABLE 1 – AAT Serum Levels

Units of Measurement Example Normal Range* Example Abnormal Result Example Normal Result
mg/dl 75-150 35 105
µM > 22 6 28
G/L 0.075-0.15 0.04 0.1

*actual normal ranges vary from laboratory to laboratory

Further testing, beyond a simple serum level, is often indicated if:

  • Identification of carriers of a single abnormal gene is desired (as in family screening)
  • The patient’s presentation is unusual (as in early onset pulmonary emphysema with a normal AAT level)
  • Confirmation of an abnormal level result is desired (an abnormal level should almost always be confirmed by a subsequent testing method)

Such further testing generally involves either phenotyping or genotyping. Phenotyping is identification of the type of circulating AAT protein by isoelectric focusing of the various isotypes of AAT in blood, plasma, or serum. Genotyping, as it is currently applied, is identification of abnormal AAT DNA by using specific probes designed to flag the most common deficient genes.

While genotyping is efficient and automated, it can only identify genes for which probes have been made. Thus, rare abnormal genotypes of AAT can be missed. The potential problem with phenotyping is that proper interpretation of phenotyping gels requires much experience. Phenotyping, when performed by an experienced scientist, is the most direct method of identifying carriers and deficient individuals, especially those with rare or unusual mutations of the AAT gene. Even so, individuals with Null genes (one of a series of AAT gene mutations that leads to the production of no detectable AAT protein) will be missed using genotyping and can often be missed without specific Null probes during genotyping.

TABLE 2 – Samples required

Type of specimen Level Phenotype Genotype
Tube of blood Yes Yes Yes 1
Dried blood spot Yes 2 Yes 3 Yes
Buccal swab No No Yes

1 Requires fresh specimen
2 Level is used for internal confirmation of result
3 Possible but not commonly done

Read patient information on testing here.