When is phenotyping indicated in the workup of alpha1-antitrypsin deficiency (AATD)?

Updated: Sep 11, 2020
  • Author: Dora E Izaguirre Anariba, MD, MPH; Chief Editor: John J Oppenheimer, MD  more...
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Test patients with low or borderline serum levels with phenotyping (serum levels < 100 mg/dL). Alpha1-antitrypsin phenotype determined by isoelectric focusing (IEF) is the most commonly used method to definitively detect the alpha1-antitrypsin phenotype that indicates a risk for AATD. It is considered the criterion standard test for identifying alpha1-antitrypsin variants, but involves complex interpretation. [3, 9, 15, 16] Use an experienced reference laboratory for this test. Phenotyping with dried blood-spot samples, by using a blood drop absorbed on special paper, permits easier transport of samples and is suitable for screening purposes, but the identification of a deficient variant should be confirmed with serum or plasma samples.

Patients and healthcare providers can obtain a free Alpha-1 Test Kit (finger-stick test) from the Alpha-1 Research Registry at (877) 886-2383, which is associated with the Alpha-1 Association. The test sample can be submitted directly to the Registry at the Medical University of South Carolina. The test screens for the most common Z and S genotypes. If more extensive testing is needed to determine an alpha1-antitrypsin level, both patient and physician are notified. There is no charge for the Alpha-1 Screening Program.

Phenotyping is required to confirm AATD. Do not initiate alpha1-antitrypsin replacement therapy without testing.

More than 100 phenotypic variants of AATD have been identified, but one phenotype, PiZZ, is responsible for nearly all cases of AATD emphysema and liver disease. PiZZ phenotype serum levels range from 3.4-7 µmol/L, about 10-20% of the reference range levels. Other phenotypes associated with alpha1-antitrypsin emphysema and liver disease include PiSZ and PiZ/Null. PiNull/Null is not associated with liver disease but is associated with alpha1-antitrypsin deficiency emphysema.

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