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Diagnosing Alpha-1
Clinical Practice Guidelines – Who Should be Tested?

The Medical and Scientific Advisory Committee of the Alpha-1 Foundation has released clinical recommendations designed to guide doctors on how to properly diagnose and treat Alpha-1 Antitrypsin Deficiency (Alpha-1) in adults.

The Clinical Practice Guidelines, based on the latest evidence and six years of work, recommend best practices on testing for Alpha-1, Alpha-1 lung and liver disease, and when augmentation therapy should be prescribed, among other recommendations. The guidelines, published in the Journal of the COPD Foundation in July 2016, are intended to update and simplify a 2003 document from the American Thoracic Society (ATS) and the European Respiratory Society on the diagnosis and management of Alpha-1.

The Clinical Practice Guidelines recommend that people with any of the following conditions/criteria should be tested for Alpha-1:

  • Chronic obstructive pulmonary disease (COPD), regardless of age or ethnicity
  • Unexplained chronic liver disease
  • Unexplained bronchiectasis
  • Necrotizing panniculitis
  • Granulomatosis with polyangiitis
  • Parents, siblings, children and extended family members of people who are identified with an abnormal alpha-1 gene should be provided genetic counseling and offered testing for Alpha-1.
  • For family testing, alpha-1-protein-level testing alone is not recommended because it does not fully characterize the risk of disease from Alpha-1
  • For family testing or diagnostic testing of people who have symptoms, genotyping is recommended for at least the S and Z alleles. Advanced or confirmatory testing should include Pi-typing, alpha-1-protein-level testing, and/or expanded genotyping
Please read the Clinical Practice Guidelines – The Diagnosis and Management of Alpha-1 Antitrypsin Deficiency in the Adult as published in the Journal of the COPD Foundation.

Download the Clinical Practice Guidelines Pocket Guide:

How to Test

It is critical to remember that Alpha-1 cannot be diagnosed by symptoms or by a medical examination alone; only a blood test will confirm Alpha-1. Testing can be conducted on a blood sample (blood draw or finger stick test). You can order a blood test to rule out Alpha-1 when doing routine blood work on your patients. The diagnosis code for Alpha-1 is 273.4. Testing for Alpha-1 is simple, quick and highly accurate.

Free Testing

To order free test kits:

Many people at risk for Alpha-1 delay being tested due to concerns about privacy of test results. The Alpha-1 Foundation offers a confidential opportunity to be tested for Alpha-1 through the Alpha-1 Coded Testing (ACT) Study. This research study is through the Alpha-1 Foundation and examines people’s thoughts and feelings about the risks and benefits associated with learning genetic information. Testing through the ACT Study is free and confidential.

For test kits or for more information, please call the Alpha-1 Foundation at (877) 228-7321 ext. 245, or email at gettested@alpha1.org.

For more information, call the Alpha-1 Research Registry toll-free at (877) 228-7321 ext. 306, or email at alpha1registry@alpha1.org.

Free Testing

For information on the Alpha-1 Foundation Genetic Counseling Program, call (877) 228-7321 ext. 326 or click here.

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.

Laboratory Results

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 alpha-1 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 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 1 – AAT Serum Levels

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

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