意大利甲状腺转运蛋白淀粉样变（ATTR）变异患病率的变化——一项全国性调查的结果

Change in prevalence of ATTR variants in Italy - Results from a National Survey.

作者信息

Fumagalli Carlo, Longhi Simone, Aimo Alberto, Argirò Alessia, Barilaro Alessandro, Biagini Elena, Biagioni Giulia, Ceccanti Marco, Cipriani Alberto, Chimenti Cristina, De Michieli Laura, Di Bella Gianluca, Emdin Michele, Graziani Francesca, Guaraldi Pietro, Imazio Massimo, Limongelli Giuseppe, Lofiego Carla, Luigetti Marco, Marazia Stefania, My Filomena, Musca Francesco, Ossola Paolo, Palladini Giovanni, Perlini Stefano, Porcari Aldostefano, Mussinelli Roberta, Musumeci Beatrice, Palmiero Giuseppe, Perfetto Federico, Russo Massimo, Tini Giacomo, Vergaro Giuseppe, Vagnarelli Fabio, Verrillo Federica, Varrà Guerino Giuseppe, Sciarrone Maria Ausilia, Sinagra Gianfranco, Merlo Marco, Obici Laura, Cappelli Francesco

机构信息

Department of Advanced Medical and Surgical Sciences, University of Campania - Luigi Vanvitelli, Naples, Italy.

Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy.

出版信息

Eur Heart J Qual Care Clin Outcomes. 2025 May 20. doi: 10.1093/ehjqcco/qcaf024.

DOI:10.1093/ehjqcco/qcaf024

PMID:40392964

Abstract

INTRODUCTION

Hereditary transthyretin amyloidosis (ATTRv) is a rare, heterogenous, inherited disorder caused by over 130 gene mutations. Its prevalence was estimated to 4.33/million in 2020 in Italy. Whether growing disease awareness and improved diagnostics may have increased national diagnoses in the last 4 years is unresolved.

METHODS

All alive ATTRv diagnoses from 2004 to 2024 from 16 Italian referral centers were retrospectively assessed and included in the analysis.

RESULTS

As of March 2024, 373 ATTRv patients were in active follow up, with an overall national prevalence increased from 2020 previous survey up to 6.33/million. The most prevalent mutations were Ile68Leu (25.1%), Phe64Leu (21.9%), Val30Met (19.3%), Glu89Gln (10.7%), and Val122Ile (6.7%). Ile68Leu, Val122Ile, and Val30Met were more common in Northern and Central Italy, while Glu89Gln and Phe64Leu were prevalent in Southern Italy. Cardiovascular phenotype was the most common (35.6%), followed by neuropathic (33.2%) and mixed phenotypes (31.2%). Referral to disease-specific therapy mirrored the change in epidemiology.

CONCLUSION

ATTRv prevalence in Italy has increased by 50% in a 4 years' time frame, with a shift towards milder disease stages and more mixed phenotypes. These changes may reflect improved disease awareness, enhanced genetic screening, and comprehensive care in specialized centers.

摘要

引言

遗传性转甲状腺素蛋白淀粉样变性（ATTRv）是一种罕见的、异质性的遗传性疾病，由130多种基因突变引起。据估计，2020年意大利的患病率为4.33/百万。在过去4年中，疾病认知度的提高和诊断方法的改进是否增加了全国的诊断病例数，目前尚无定论。

方法

对意大利16个转诊中心2004年至2024年所有存活的ATTRv诊断病例进行回顾性评估，并纳入分析。

结果

截至2024年3月，373例ATTRv患者正在接受积极随访，全国总体患病率从2020年的上次调查结果上升至6.33/百万。最常见的突变是Ile68Leu（25.1%）、Phe64Leu（21.9%）、Val30Met（19.3%）、Glu89Gln（10.7%）和Val122Ile（6.7%）。Ile68Leu、Val122Ile和Val30Met在意大利北部和中部更为常见，而Glu89Gln和Phe64Leu在意大利南部较为普遍。心血管表型最为常见（35.6%），其次是神经病变型（33.2%）和混合型（31.2%）。转诊接受疾病特异性治疗反映了流行病学的变化。