To quantify the prevalence and timing of polyneuropathy symptoms among individuals with confirmed transthyretin (ATTR) amyloidosis, and to evaluate associations among polyneuropathy characteristics, disease severity, and healthcare utilization, stratified by genotype.

Hereditary transthyretin amyloidosis (ATTRv) is an autosomal dominant condition historically characterized by organ predominance such as cardiomyopathy (ATTR-CM), polyneuropathy (ATTR-PN), or both. Transthyretin variants such as V50M and A97S are typically linked to polyneuropathy (PN) predominance while V142I is linked to cardiomyopathy (CM) dominant disease. Emerging evidence suggests these ATTR variants have overlapping phenotypes.

GeneVA (Genetic Variants in ATTR) is a retrospective observational study integrating data from the Clarivate Real World Data, American Community Survey, and the ATTR Compass Genetic Testing Program. Individuals with ATTR-CM were classified as hereditary or wild type. PN symptom prevalence prior to ATTR-CM diagnosis, subsequent ATTR-PN diagnosis, symptom categories (neuropathic, motor, sensory, autonomic), one-year hospitalization rates, and time from PN symptom onset to ATTR-CM diagnosis were examined. Analyses were stratified by genotype.

Among 3,691 ATTR-CM patients, 44% had documented PN symptoms before ATTR-CM diagnosis, with similar prevalence by genotype (V142I, 43%; T80A, 42%; V50M, 54%).  For most patients (57%), PN symptoms were present more than 2 years (< 1 year, 26%; 1-2 years, 16%).  Motor (26%) and autonomic (16%) symptoms were most common; 36% had symptoms spanning at least 2 categories (V142I, 38%; T80A, 56%; V50M, 50%).  Overall, 11% subsequently received an ATTR-PN diagnosis, with higher rates in hereditary (V142I, 23%; T80A, 36%; V50M, 27%) versus wild type (7%) disease.  V142I carriers had the highest one-year hospitalization rate post ATTR-CM diagnosis (41%).