Hereditary transthyretin amyloidosis (ATTRv) arising from the TTR gene V30M variant (ATTRV30M) manifests in two distinct phenotypes: early-onset (before age 50 years) with polyneuropathy and late-onset (after age 50 years) with a mixed phenotype, encompassing neurological and cardiac manifestations (ATTR-CM). Comparative studies examining ATTR-CM in early and late ATTRV30M have typically involved patients post-diagnosis, with early-onset individuals being younger.

This study aimed to compare ATTR-CM in early and late ATTRV30M at similar ages.

Medical records of 370 ATTRV30M patients were analysed (median follow-up: 3.6 years), data were analysed by 10-year age groups. Confirmed ATTR-CM was defined by a positive DPD scan (Perugini score≥2), OR positive biopsy with unexplained interventricular septum>12mm, CMR suggestive of cardiac amyloidosis or Perugini 1). Suspected ATTRv-CM was defined in case of cardiac abnormalities that did not meet the confirmed ATTRv-CM criteria.

Among V30M carriers, 138 had early-onset polyneuropathy, 113 late-onset polyneuropathy, and 119 were asymptomatic carriers. ATTR-CM was confirmed in 16.7% of early-onset, 75.2% of late-onset, and 3.9% of asymptomatic carriers. ATTR-CM frequency increased with age. In a given age group, ATTR-CM degree was identical in early and late-onset groups (Fig. 1). Conversely, asymptomatic carriers showed lower ATTR-CM frequency (P=0.001 in the 50–59yo age group, P<0.001 in the 60–69yo age group). Late-onset patients had significantly higher life expectancy than early-onset patients (83yo vs. 62yo, respectively; P<0.001).

In a comparable age group, ATTR-CM extent is consistent in early and late-onset ATTRV30M. ATTR-CM penetrance rises with age, and both early and late-onset ATTRV30M exhibit a mixed phenotype. Neurological manifestations precede ATTR-CM onset.