Transthyretin Amyloidosis Due to a Rare TTR Val142del Deletion With Relatively Early Clinical Manifestations

Abstract

Background Hereditary transthyretin amyloidosis shows marked phenotypic heterogeneity. In-frame deletions at codon 142 are exceedingly rare, and their cardiac expression remains poorly characterized. Case Summary A 62-year-old man presented with progressive neuropathy, autonomic dysfunction, weight loss, and recurrent syncope. Multimodality imaging demonstrated concentric hypertrophy with preserved ejection fraction, apical sparing on strain, diffuse late gadolinium enhancement with increased extracellular volume, and grade III uptake on 99mTc-pyrophosphate scintigraphy. Monoclonal gammopathy was excluded. Genetic testing identified a heterozygous the transthyretin p.Val142del deletion. Autonomic testing confirmed orthostatic hypotension with impaired chronotropic response. Heart failure therapy and tafamidis led to symptomatic improvement. Cascade screening identified 2 asymptomatic carriers. Discussion Unlike the common Val142Ile substitution, this deletion appears associated with earlier penetrance and multisystem involvement. Take-Home Messages Rare transthyretin deletions may cause aggressive hereditary transthyretin amyloidosis. Early recognition and family screening are essential.