Manifestations of A Rare Italian Variant of Transthyretin Amyloidosis

Abstract

Background Hereditary forms of amyloidosis are rare, but diagnosis will impact the treatment course of the patient and have lasting implications for other family members. Case 77 year old gentleman of Italian descent with a history of systolic heart failure (ejection fraction of 41%), hypertension, bilateral carpal tunnel syndrome, persistent atrial fibrillation (pulmonary vein isolation in 2013), history of mixed aortic valve disease status post 24 mm homograft presents with homograft degeneration. He subsequently underwent an aortic valve replacement with #23 CE valve and a 30 mm hemashield graft, mitral valve replacement and Left atrial appendage ligation. Left atrial appendage and mitral valve tissue were positive for amyloid on thioflavin S stain and immunohistochemical staining with strong reactivity to transthyretin. TTR genotyping confirmed an Italian variant c.252T>G; p.Phe84Leu (old nomenclature Phe64Leu). A technetium pyrophosphate (TcPYP) scan was not suggestive of cardiac amyloidosis (H/CL ratio G; p.Phe84Leu mutation. He has been referred to neuromuscular clinic for further evaluation and potential initiation of a medical therapy. Conclusion The two brothers highlight some of the difficulty associated with the diagnosis of amyloidosis given its variable clinical phenotype. Additionally, it is known that myocardial uptake in bone compound scintography scans can be falsely negative for unclear reasons in patients with c.252T>G; p.Phe84Leu mutations. Lastly, the isolated left atrial uptake on TcPYP scans should be further investigated as an early manifestation of cardiac amyloidosis.