Hereditary Transthyretin Amyloidosis in Brazilian Amazon Caused by a Globally Rare Variant Predominant in Asia.

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) exhibits marked phenotypic heterogeneity. The p.Asp58Ala variant is globally rare and has not been reported in major Brazilian epidemiologic studies. CASE SUMMARY: We report 10 patients with ATTRv-p.Asp58Ala, including 6 index cases and 4 identified through family screening. Mean left ventricular ejection fraction was 64.7%, with a mean interventricular wall thickness of 14.1 mm and a mean posterior wall thickness of 12.9 mm. Mixed cardiac and neurologic involvement predominated (60%), followed by asymptomatic (30%) and isolated cardiac (10%) phenotypes. Among 7 patients under follow-up, 2 receive tafamidis and 1 receives inotersen. DISCUSSION: Similar to Korean and other Asian cohorts, mixed phenotypes predominated, although our series showed substantial cardiac involvement and significant mortality. TAKE-HOME MESSAGES: p.Asp58Ala is a rare ATTR variant, previously described mainly in Asian populations. Its identification in the Amazon region suggests a possible previously unreported regional clustering in Brazil.