α₁-Antitrypsin Deficiency, DNA Analysis

Whole blood, amniotic fluid, chorionic villus sample (CVS) (submission of maternal blood is required for fetal testing), or Labcorp buccal swab kit (buccal swab collection kit contains instructions for use of a buccal swab)

7 mL whole blood, 10 mL amniotic fluid, 20 mg CVS, or Labcorp buccal swab kit

3 mL whole blood, 5 mL amniotic fluid, 10 mg CVS, or two buccal swabs

Lavender-top (EDTA) tube, yellow-top (ACD) tube, sterile plastic conical tube or two confluent T-25 flasks for fetal testing, or Labcorp buccal swab kit

Aids in establishing a diagnosis of individuals suspected to have alpha-1 antitrypsin deficiency

Results should be combined with clinical information for the most accurate interpretation. Molecular-based testing is highly accurate, but as in any laboratory test, rare diagnostic errors may occur. False positive or false negative results may occur for reasons that include genetic variants, blood transfusions, bone marrow transplantation, somatic or tissue-specific mosaicism, mislabeled samples, or erroneous representation of family relationships.

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

Two variants are analyzed: c.1096 G>A (p. Glu366Lys), commonly referred to as the Z allele or PI*Z c.863 A>T (p.Glu288Val), commonly referred to as the S allele or PI*S. DNA analysis of the S and Z alleles in the SERPINA1 gene (NM_000295.4) is performed by multiplex allele-specific PCR amplification followed by gel electrophoresis.

Alpha-1 antitrypsin deficiency is an autosomal recessive metabolic disorder with variable severity and age at onset. Signs and symptoms may include increased risk for chronic obstructive lung disease that typically manifests after age 30, liver disease, and liver cancer. Liver disease can be present in infancy as neonatal cholestasis (jaundice) or in adulthood as cirrhosis and fibrosis. Lung and liver disease may be accelerated by environmental exposures such as smoking and excessive alcohol use. Established treatments for COPD and emphysema are used to treat lung disease; lung and/or liver transplantation may be an option for those with severe disease. Intravenous augmentation therapy may be available for patients who meet criteria. The ZZ and SZ genotypes account for more than 95% of individuals with severe alpha-1 antitrypsin deficiency. To rule out other variants, further testing of symptomatic individuals heterozygous for one variant (S or Z) or with negative results may include phenotyping (PI typing), AAT level testing, and/or expanded genotyping. Genetic coordinators are available for health care providers to discuss results and for information on how to order additional testing, if desired, at 1-800-345-GENE.