Alpha-1-Antitrypsin (SERPINA1) Enzyme Concentration and 2 Mutations with Reflex to Alpha-1-Antitrypsin Phenotype

Background Information for A1A (SERPINA1) Enzyme Concentration and 2 Mutations with Reflex to A1A Phenotype:
Characteristics of Alpha-1-Antitrypsin (AAT) Deficiency: Coughing, wheezing, bronchiectasis, chronic obstructive pulmonary disease, emphysema, and cirrhosis.
Incidence: 1 in 3000 to 5000 North American individuals.
Inheritance: Autosomal recessive.
Cause: Two pathogenic mutations in the SERPINA1 gene on opposite chromosomes.
Clinical Sensitivity: 95 percent.
Mutations Tested: S allele (c.791A>T) and Z allele (c.1024G>A).
Methods: Genotyping performed by polymerase chain reaction (PCR) and fluorescence monitoring; AAT protein concentration measured using immunoturbidmetric assay; phenotyping performed by isoelectric focusing electrophoresis. Genotyping and AAT serum protein concentration determination are performed on all specimens. Protein phenotyping is only performed on specimens that have AAT protein concentrations of less than 90 mg/dL and are not homozygous or compound heterozygous for the S or Z deficiency alleles by genotyping. 
Analytical Sensitivity and Specificity: 99 percent.
Limitations: SERPINA1 mutations, other than the S (c.791A>T) and Z (c.1024G>A) alleles, will not be detected. Diagnostic errors can occur due to rare sequence variations.

This test was developed and its performance characteristics determined by ARUP Laboratories. It has not been cleared or approved by the US Food and Drug Administration. This test was performed in a CLIA certified laboratory and is intended for clinical purposes.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.