Algorithm for interpreting SERPINA1 genetic testing

SNP: single nucleotide polymorphism; AAT: alpha-1 antitrypsin; AATD: alpha-1 antitrypsin deficiency; CLIA: Clinical Laboratory Improvement Amendments; COPD: chronic obstructive pulmonary disease; PFTs: pulmonary function tests; CBC: complete blood count.

* Adequate testing depends on the individual's family history and personal history.

• SERPINA1 genetic testing – Genetic testing is appropriate for individuals with a positive family history of AATD or carrier status as well as those with unexplained COPD, liver disease, low AAT level, or other findings associated with AATD. If there is a family history of AATD and the familial variant is known, testing must include that variant. If there are symptoms or clinical findings potentially attributable to AATD, full SERPINA1 gene sequencing is required.
• AAT level – AAT testing (serum level) is appropriate for individuals with a positive family history of AATD, an abnormal SERPINA1 genetic test, or clinical findings potentially attributable to AATD. The normal reference range for AAT is generally >100 mg/dL (>20 micromol/L). Ideally, the AAT level is tested when an individual is well and not pregnant, as inflammation and pregnancy can increase AAT levels, especially in individuals who have at least one normal allele.

An individual with a low AAT level should have SERPINA1 genetic testing; an individual with abnormal genetic testing should have a serum AAT level. If there is a discrepancy between genotype and AAT level, specialist input and full gene sequencing is usually required to resolve the discrepancy.

¶ Specialists include pulmonologists, hepatologists, genetics professionals, and others. The choice among them depends on:

• Clinical findings
• Family history
• AAT level
• Specific alleles identified

Δ Management includes regular PFTs every 6 to 12 months, liver biochemical tests and CBC with platelet count every 6 to 12 months, liver elastography and possible ultrasound, as well as other assessments as appropriate to clinical status. Refer to UpToDate for details of the evaluation and management of AATD.