TTR Variant p.Ala65Val Causing Early-Onset Hereditary Transthyretin Amyloidosis With Mixed Cardiac and Neuropathic...

Variant transthyretin amyloidosis (ATTRv) remains undercharacterized in Latin America, with limited awareness of its regional mutational diversity.

A 48-year-old Peruvian man presented with syncope, exertional dyspnea, weight loss, and lower extremity paresthesia. Multimodality evaluation demonstrated severe infiltrative cardiomyopathy, small fiber and autonomic neuropathy, and peripheral nerve hypertrophy. Genetic testing identified a heterozygous pathogenic p.Ala65Val transthyretin variant, confirming ATTRv. No transthyretin-targeting therapies are currently accessible in Peru.

To our knowledge, only 1 prior case harboring this variant has been reported, in a European patient with a late-onset presentation. Our patient exhibited an early-onset mixed cardiac and neuropathic phenotype, broadening the clinical spectrum of this rare variant.

This case highlights the phenotypic diversity of ATTRv and underscores the critical unmet need for disease-modifying therapy access and greater inclusion of Latin American patients in clinical trials.