First Reported Case of Dual Hereditary Gelsolin and Transthyretin Wild-Type Cardiac Amyloidosis in a Man in his late 40s

Abstract

Amyloidosis is a group of disorders characterized by abnormal deposition of amyloid proteins in various tissues and organs, leading to progressive organ dysfunction. With over 40 precursor proteins linked to amyloid formation, identification of the amyloid type is critical to guide treatment. A man in his late 40s presenting with heart failure was diagnosed with cardiac amyloidosis based on an endomyocardial biopsy. Amyloid typing performed on the heart biopsy at Mayo Clinic Laboratories using differential laser microdissection and shotgun proteomics with mass spectrometry reported gelsolin amyloid (AGel) deposits exclusively in the vasculature and transthyretin amyloid deposits exclusively within the interstitium. Mutational analysis identified a novel p.Y474N in the gelsolin gene, establishing a diagnosis of hereditary AGel amyloidosis. Transthyretin gene mutations were absent, confirming a concurrent diagnosis of acquired transthyretin wild-type amyloidosis. The patient, who had been treated with guideline-directed medical therapy since his initial presentation, was subsequently started on tafamidis, with subsequent improvement of his ejection fraction after 6-7 months. Although rare, 2 different amyloid types may arise in the same anatomic site. Identification of all amyloid types is crucial for optimal patient management. In this case, the co-existence of 2 rare amyloid types (AGel with a novel mutation coupled with ATTRwt in a patient under 50 years of age) in mutually exclusive anatomic compartments in the same cardiac biopsy raises the possibility that an unknown systemic factor may play a role in amyloidogenesis in dual amyloid cases.