The Testing for Alpha-1 Antitrypsin Deficiency

The Basics The History The Genetic Path The Symptoms The Phenotypes The Treatments The Testing

Lab Studies

Serum AAT levels

To identify disease, determine serum AAT levels.
Testing is readily available in most clinical laboratories and is underutilized. Alpha-1 Test Kits are available by mail for physicians and/or patients.
Clinical features that suggest the possibility of AAT deficiency and the need for serum testing include emphysema at an early age, emphysema in a nonsmoker (or light smoker), a family history of emphysema, emphysema of the lower lungs (as determined by chest radiograph), adult-onset asthma, and recurrent bronchitis.
Serum testing is a screening procedure. Test most patients with chronic or recurrent respiratory symptoms (dyspnea, cough, wheezing) at least once.
Most hospital laboratories report serum AAT levels in mg/mL, with a reference range of approximately 100-300 mg/mL. Levels less than 80 mg/mL suggest a significant risk for lung disease.
Reference laboratories usually report the serum levels in micromolar concentration, with a reference range of 20-60 mmol/L and a threshold level for emphysema at 11 mmol/L.

Phenotyping

Test patients with low or borderline serum levels with phenotyping. Use an experienced reference laboratory for this test. Free genetic screening kits are available through Telacris Direct at 800-288-8371, and samples can be processed for free at the AAT Deficiency Detection Center, University of Utah, 801-328-4662. Baylor will also test for the AAT gene and will send the bill to your insurance company, if approved.
Phenotyping is required to confirm the presence of AAT deficiency. Do not initiate AAT replacement therapy without testing.
More than 100 different phenotypic variants of AAT deficiency have been identified, but 1 phenotype, PiZZ, is responsible for nearly all cases of AAT emphysema and liver disease. PiZZ phenotype serum levels range from 3.4-7 mmol/L, about 10-20% of the reference range levels.

Functional assay of alpha1 antiprotease

In rare circumstances, a third test is utilized to evaluate a patient with clinical features that are highly suggestive of AAT deficiency but whose serum levels are within the reference range.
Specialized laboratories can perform a functional assay of alpha1 antiprotease, which measures the ability of the patient's serum to inhibit human leukocyte elastase. Such a defect is rare.
Evaluate hepatic function in patients with low or borderline levels of AAT. Measure serum transaminases, bilirubin, albumin, and routine clotting function (activated partial thromboplastin time and international normalized ratio).

Imaging Studies

Chest radiograph

AAT deficiency emphysema produces a hyperlucent appearance because healthy tissue has been destroyed.
The process is not uniform; certain areas are affected more than others.
Affected regions also are described as oligemic because they lack the normal rich pattern of branching blood vessels.
An unusual characteristic in AAT emphysema is the basilar distribution of abnormalities found in approximately 75% of PiZZ patients; however, cigarette smoking is associated with more severe apical disease.

High-resolution CT scan

High-resolution CT (HRCT) scan of the chest demonstrates widespread abnormally low attenuation areas resulting from a lack of lung tissue. As in smoking-related emphysema, the appearance has been described as a simplification of lung architecture. As tissue is lost, pulmonary vessels appear smaller, fewer in number, and farther spread apart.
Mild forms of AAT disease can be missed by HRCT scan, but, when the disease is moderate, discerning the panlobular nature of the process and the characteristic lower zone predominance is possible.
Very severe forms may be indistinguishable from severe centrilobular emphysema.

Other Tests

PFT

The severity of emphysema is best documented with standard, PFTs (pulmonary function tests). Spirometric determination of forced vital capacity (FVC) and forced expired volume in 1 second (FEV₁) are essential. Determining lung volume (preferably by plethysmography) and measuring diffusing capacity provide additional valuable information.
Patients who are symptomatic at the time of diagnosis usually demonstrate moderate-to-severe airflow obstruction with an FEV₁ in the range of 30-40% of the predicted value. Also, reduced vital capacity and increased lung volumes secondary to air trapping (residual volume >120% of predicted value) usually are present. Diffusing capacity values are reduced substantially (<50% of predicted value) in most symptomatic patients. AAT-deficient individuals who are identified by screening programs or because a relative has been diagnosed with the disease may have few or no abnormalities.(1)

Order Alpha-1 Test Kits from:

University of Florida

DNA & Tissue Bank of Florida

Alpha One International Registry (AIR)

References:
1. Paul Fairman M.D. "Alpha-1 Antitrypsin Deficiency." eMedicine 14 Feb. 2002. 5 Nov. 2002 <http://www.emedicine.com/med/topic108.htm#section~pictures>

Disclaimer
This site is not a substitute for genuine medical advice. The information provided by this site is for the education and support of people diagnosed with A1Ad and others wishing to know more about this condition. It is intended that this site will enable you to ask your own doctors the right questions about your condition.