Hereditary Transthyretin Amyloidosis in Austria: Clinical, Genetic, and Demographic Insights from a Nationwide Cohort

TL;DR

This study provides updated insights into the clinical, genetic, and regional characteristics of hereditary transthyretin amyloidosis in Austria, highlighting increased detection and regional clustering.

Contribution

The study presents the first nationwide Austrian ATTRv registry update, revealing new genetic and demographic trends in a nonendemic region.

Findings

The number of genetically confirmed ATTRv cases in Austria has more than doubled compared to previous data.

Twenty-three TTR variants were identified, with p.His108Arg being the most frequent pathologic variant.

Significant regional clustering of p.His108Arg was observed in Vienna and Lower Austria.

Abstract

Background/Objectives: Hereditary transthyretin amyloidosis (ATTRv) is a heterogeneous multisystem disease caused by pathogenic transthyretin gene (TTR) variants. Increased awareness and availability of disease-modifying therapies have resulted in increased diagnoses, even in previously nonendemic regions. The aim of this study was to update the nationwide Austrian ATTRv registry by characterizing the clinical, genetic, and regional distribution of TTR variants. Methods: This multicenter, observational analysis examined ATTRv cases diagnosed in Austria between 2014 and 2025. Individuals were included according to the presence of pathogenic or likely pathogenic variants or variants of uncertain significance (VUSs) in TTR. Results: In total, 100 individuals were identified, including symptomatic and asymptomatic carriers. Compared with our previously presented data, the number of genetically confirmed ATTRv cases has more than doubled. Twenty-three TTR variants were identified. The most frequent pathologic variants were p.His108Arg (26%), p.Ile127Phe (11%), and p.Thr69Ile (9%), while p.Val113Leu (9%) represented the most frequent VUS. Significant regional clustering of p.His108Arg was documented in Vienna and Lower Austria. Other findings included a rising number of p.Val142Ile carriers and phenotypically relevant VUSs in 20 patients. Conclusions: Our findings revealed an increasing detection rate of ATTRv in a nonendemic European region. These data underscore the importance of multidisciplinary evaluation, cascade testing, and long-term monitoring to improve early diagnosis and timely management in hereditary amyloidosis.

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