Resources for Physicians - Diagnosis and Testing

Updated May 5, 2010

The World Health Organization, the American Thoracic Society and Alpha-1 Canada recommend that everyone with COPD be tested for alpha-1 antitrypsin deficiency.

Clinical Diagnosis

A1AD is suspected in individuals with evidence of:

• pulmonary disease (i.e., emphysema, asthma, persistent airflow obstruction, and/or chronic bronchitis) and/or
• evidence of liver disease at any age, including obstructive jaundice in infancy
• individuals with bronchiectasis
• A1AD is also observed rarely in individuals with Wegener granulomatosis and necrotizing panniculitis

The diagnosis of A1AD relies on the following:

• demonstration of low plasma concentration of alpha-1 antitrypsin (AAT)

AND

• observation of a deficient variant of the protein AAT by protease inhibitor (PI) typing

OR

• detection by molecular genetic testing of mutations in both copies of SERPINA1, the gene encoding AAT.

Measurement of AAT level is the first step.

The diagnosis of A1AD relies on demonstration of low plasma concentration of AAT, followed by (when low) either observation of a deficient variant of the protein AAT by protease inhibitor (PI) typing or detection of mutations in both copies of the gene SERPINA1, which encodes AAT. PI*Z is the most common deficiency allele. Ninety-five percent of A1AD results from the presence of two Z alleles. Genetic testing is clinically available.

How to get your patient tested for Alpha-1 antitrypsin deficiency in Canada

Testing for alpha-1 antitrypsin deficiency: Measurement of AAT level is the first step

The diagnosis of A1AD relies on demonstration of low plasma concentration of AAT, followed by (when low) either observation of a deficient variant of the protein AAT by protease inhibitor (PI) typing, genotyping or detection of mutations in both copies of the gene SERPINA1, which encodes AAT. PI*Z is the most common deficiency allele. Ninety-five percent of A1AD results from the presence of two Z alleles (PIZZ).

Phenotyping or genotyping are usually done only when previously measured AAT is 1.5 g/L or less (or below the normal mean for the testing laboratory), OR the patient is a first-degree relative/spouse of a known AAT deficient subject. A request for PI typing when ordered separately should specify the previous result or the subject’s name and relationship for phenotyping to proceed.

Confirmatory Testing for Alpha-1 Antitrypsin Deficiency in Canada

The following information about testing applies in all provinces except Alberta. For information on testing in Alberta, please click here.

Testing serum levels of alpha-1 antitrypsin (AAT) continues to be easily available throughout Canada. Following a low serum AAT result, confirmatory testing should be carried out to determine if the low level is the result of a genetic abnormality. In Canada there are four validated laboratories that can carry out the confirmatory testing. They are located at St. Paul’s Hospital in Vancouver, the Royal Victoria Hospital and CHUM - Hôpital Notre-Dame, both in Montreal, and Credit Valley Hospital in Mississauga. Through collaboration, these four laboratories have developed a comprehensive testing algorithm to confirm or rule out the diagnosis of alpha-1 antitrypsin deficiency. The AAT serum level threshold for confirmatory testing used by these two laboratories is 1.15 g/L. Individuals with a serum level less than 1.15 g/L would be processed for confirmatory testing.

Dr. Andre Mattman
St. Paul’s Hospital
Dept. of Pathology & Laboratory Medicine
1081 Burrard Street,
Vancouver, British Columbia, V6Z 1Y6
Phone: 604-806-8810

Dr. Marsha Speevak  (mspeevak@cvh.on.ca)
Credit Valley Hospital
Clinical Genetics Laboratory, 2200 Eglinton Avenue West, Rm 2H144
Mississauga, Ontario L5M 2N1
Phone: 905-813-1100 x6288 Fax: 905/813-3854

Dr. Brian Gilfix
Central Reception, C-6
MUHC-Royal Victoria Hospital
687 Pine Avenue West,
Montreal, Quebec, H3A 1A1
Phone: 514-934-1934 x 34410

Dr. Jean-Pierre Émond, (jean.pierre.emond.chum@ssss.gouv.qc.ca)
Biochimiste clinique
CHUM - Hôpital Notre-Dame
Département de biochimie
Pavillon Deschamps, 6ème étage
1560, rue Sherbrooke est
Montréal, QC H2L 4M1

Individuals with serum level above this threshold would not normally proceed through the testing algorithm unless there is a strong suspicion of alpha-1 deficiency. This information should be outlined in the requisition form by the physician and provided to the testing laboratories.  In a stepwise fashion, the laboratory will run a series of tests to characterize the individual’s alpha-1 genetics. This includes a genotyping assay to identify the presence of the common deficiency alleles, followed by phenotyping (isoelectric focusing) and finally, if required, full gene sequencing of the individual’s alpha-1 gene.

Currently there is no cost to be tested. The physician simply needs to complete the requisition form for alpha-1 genetic testing, and have one tube of the individual’s blood and one tube of frozen serum shipped to one of the testing labs. Following analysis, a detailed response is provided to the physician within 30 days that outlines the results of the tests.

AlphaKit Blood Drop Cards

Another option is the AlphaKit blood drop cards. Grifols, the makers of Prolastin®-C, have developed and received government approval for an Alpha-1 test kit. Once the physician has determined that the patient’s AAT level is low (1.5 g/L or less, or below the normal mean for the testing laboratory) he or she can call the bilingual call-centre at 1-877-3 ALPHA1 (1-877-325-7421), to order a test kit. Once your doctor receives the kit, three dry blood drop samples are taken then mailed to a testing facility at the University of Florida. Within two to three weeks the physician will receive the results through the mail.

It is important to understand that while the patient’s personal information and test results will only be divulged to their physician, unlike test kits that were available a few years ago, these kits are not anonymous. Since the kits and results can only be sent to your physician, he or she will place your results in your medical file (please see our web page on “Ethical Issues” to learn about the ethical implications of this procedure).

Grifols provides the specimen collection kit (including a postage paid mailer pre-addressed to the testing facility) and the testing services of the University of Florida Alpha1 Lab at no charge. This program is being managed and operated for Grifols by third parties; Grifols will not have access to anyone’s test results.

Early detection of Alpha-1 is critically important. Once a patient knows they have Alpha-1 they can make important lifestyle changes and receive treatment from their physician to slow the progression of the disease. The only way to detect Alpha-1 is through testing. We encourage you to take charge of your healthcare, take advantage of this speedy, easy process and contact your physician with this critical information. Whether you have been diagnosed or are awaiting testing, please keep your physician informed. Print this page and bring it with you to your next doctor’s appointment. And please, inform your close blood relatives that testing and diagnosis is now quick, easy and free.

Should you have any questions do not hesitate to contact Jim at 1-888-669-4583 or jim.mundy@alpha1canada.

Interpretation of Results

The normal plasma concentration of AAT is 80% to 120% of normal. Mean is 1.3 g/L (range: 1.06 g/L to 1.58 g/L).

For adults with the PI ZZ genotype. The concentration is usually 13%to 23%of normal (mean: 18%±5%of normal).

For children with the PI ZZ genotype and liver disease the plasma concentration can be as high as 40% of normal.

Protease Inhibitor (PI) Types

• PI ZZ: Plasma concentration of AAT approximately 18% of normal (0.23 g/L)
• PI SZ: Not usually associated with a high risk for liver or lung disease; higher risk of developing COPD among smokers
• PI MZ: Slightly increased risk for decreased lung function
• PI MM: Observed in normal individuals with normal plasma concentration of AAT

For more information about testing contact Alpha-1 Canada at 1-888-669-4583 or jim.mundy@alpha1canada.ca.  The Alpha-1 Canadian Registry provides information on research and testing, you can visit their website at www.alpha1canadianregistry.com or call 1-800-352-8186.      

Prevalence

A1AD affects all racial groups worldwide. It is most common among Caucasians and least common in Asian and black populations, among whom rare deficiency variants other than PI ZZ also occur. The prevalence of A1AD in the white population of North America ranges between one in 5,000 and one in 7,000.

 

This website is designed to support, not replace, the relationship that exists between you and your physician. It is not the intention of this website to provide specific medical advice but rather to provide the Canadian Alpha-1 Community with information to better understand their health and their diagnosed disorder. Specific medical advice will not be provided and Alpha-1 Canada urges you to consult with a qualified physician for diagnosis and for answers to your personal questions.