Implementation of SERPINA1 Next-generation Sequencing and Bretzi in Alpha-1 Antitrypsin Deficiency




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Alpha-1 Antitrypsin deficiency (AATD) is a common hereditary disease in families that have autosomal codominant patterns composed of two different variants of alleles, and generally are suspected in young patients (age 25-50) with symptoms of pulmonary emphysema or chronic obstructive pulmonary disease (COPD), with treatment consisting of either augementation therapy with IV purified AAT or symptomatic treatment. It is currently recommended to support initial quantitative serum AAT level measurements with some sort of qualitative testing for comprehensive diagnosis and risk assessment.

Case Presentation:

We report the case of a caucasian 51-year-old female with no significant history of smoking, occupational chemical exposure, and exposure to birds, who presented to the clinic with complaint of persistent dry frequent coughs with associated shortness of breath (SOB), headache, and difficulty sleeping. At the time of initial presentation the patient reports taking Azelastine HCI, Benzonatate, Albuterol Sulfate, ProAir HFA, Zafirlukast, and Fluticasone Propionate with no improvement of symptoms. Initial workup found significant hyperinflation on Chest X-ray and Pulmonary Functions Tests (PFT) and AAT deficiency testing was initiated based on clinical guidelines. Advanced testing with SERPINA1 next generation sequencing was ordered in conjunction with serum AAT levels to confirm the diagnosis and the patient was started on a month course of Trelegy with minimal improvement of symptoms. A sample of Bretzi was given and on follow-up, patient endorsed resolution of symptoms with improved quality of life and denied any coughing, wheezing, SOB, chest pain, sinus congestion, runny nose, headache, or dizziness.


This case illustrates a typical clinical presentation of AATD; we conclude that the addition of SERPINA 1 next generation sequencing (FDA determined no need for clearance) as a confirmatory measure and resolution of symptoms with a course of Bretzi, a 3-in-1 maintenance COPD medication cleared by the FDA in 2020, suggest the efficacy of including these relatively new modalities in the treatment of future AATD patients.