Alpha-1 antitrypsin deficiency associated with rare SERPINA1 alleles p.(Phe76del) and p.(Asp280Val): A family study

Abstract

This report describes family members with alpha-1 antitrypsin (AAT) deficiency arising from two rare alleles of SERPINA1 – p.(Phe76del) and p.(Asp280Val) along with the more common deficiency allele, Pi*Z. The index case, a 51-year-old female presented with cough, bloody sputum, fever, weight loss and night sweats. In addition to a respiratory infection, scans revealed bronchiectasis and bronchiolitis without emphysema. Her AAT level was 30 mg/dL and genetic testing revealed a Pi*Z/p.(Phe76del) genotype. Follow up testing of her relatives revealed the rare p.(Asp280Val) variant as well. AAT deficiency remains underdiagnosed. Early detection and intervention could improve quality of life and outcomes.