Phénotype de la maladie de Fabry au cours des 20 dernières années : analyse d’une cohorte de 107 patients et focus sur le variant F113L

IF 0.9 4区医学 Q3 MEDICINE, GENERAL & INTERNAL

Revue De Medecine Interne Pub Date : 2025-10-01 DOI:10.1016/j.revmed.2025.07.007

Olivier Lidove , Benjamin Subran , Camille Montardi , Quentin Besset , Clara Mellot , Julien Aki Baba , Chadi Azar , Jonathan London , Philippe Charron , Catherine Caillaud , Foudil Lamari , Olga Azevedo , Wladimir Mauhin

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引用次数: 0

Abstract

Introduction

Fabry disease (FD, #OMIM 301 500) is an X-linked lysosomal disorder. Prior to the 2000s, it was considered a male-only disease. The emergence of two intravenous enzymotherapies (2001) and then of an oral chaperone molecule (2016) brought this rare disease into the spotlight. This work describes our cohort of patients with FD and aims to analyze the predominant classical and cardiac phenotypes (including the F113L variant).

Methods

In December 2022, we retrospectively analyzed all patients with FD managed within the lysosomal disease reference center. We describe and compare phenotypes before and after 2012.

Results

Our cohort included 107 patients (48 men-M, 59 women-F). The F113L variant accounted for 18% of cases, all in patients from Portugal. Before 2012, of the 45 patients followed (21M, 24F), 29 presented a classic form with acroparesthesia and cornea verticillata (64%) and 16 a predominantly cardiac form (36%), including 4 (1MH, 3F) with F113L variant. Eight patients died of cardiac complications (5M, 3F). After 2012, 62 new patients were included (27M, 35F), with 18 classic forms (29%) and 44 predominantly cardiac forms (71%). Of the 44 patients with a predominant cardiac form, 15 (9M, 6F) carried the F113L variant. Two men with the F113L allele had a severe form of the disease, requiring pacemaker implantation following cardiac arrest following complete atrioventricular block in one (aged 48), and registration for renal transplantation at age 64 in the other.

Conclusion

FD affects both men and women. The predominantly cardiac phenotype is now the most fequent. It is also observed in the majority of patients with the F113L variant. Extra-cardiac involvement is possible and should be investigated if this variant is detected.

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[法布里病过去20年：107例患者队列分析，重点关注F113L变异]。

简介：Fabry病（FD, #OMIM 301 500）是一种x连锁溶酶体疾病。在本世纪头十年之前，它被认为是男性独有的疾病。两种静脉内酶疗法（2001年）和口服伴侣分子（2016年）的出现使这种罕见疾病成为人们关注的焦点。这项工作描述了我们的MF患者队列，旨在分析主要的经典和心脏表型（包括F113L变体）。方法：2022年12月，我们回顾性分析了溶酶体疾病参考中心管理的所有MF患者。我们描述并比较了2012年前后的表型。结果：我们的队列包括107例患者（48例男-男，59例女-女）。F113L变体占病例的18%，所有患者都来自葡萄牙。2012年以前，在随访的45例患者（21M, 24F）中，29例表现为典型的肢端感觉异常和轮胎性角膜（64%），16例表现为心脏型（36%），其中4例（1MH, 3F）为F113L变异。8例患者死于心脏并发症（5M, 3F）。2012年后，新纳入62例患者（27M, 35F），其中18例为经典型（29%），44例为心脏型（71%）。在44例主要心脏形式的患者中，15例（9M, 6F）携带F113L变体。两名携带F113L等位基因的男性患有严重的疾病，其中一名患者（48岁）在完全房室传导阻滞后心脏骤停后需要植入起搏器，另一名患者在64岁时登记接受肾移植。结论：MF对男性和女性均有影响。以心脏为主的表型现在是最常见的。在大多数F113L变异患者中也观察到这种情况。心脏外受累是可能的，如果检测到这种变异，应进行调查。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Revue De Medecine Interne 医学-医学：内科

CiteScore

0.70

自引率

11.10%

发文量

526

审稿时长

37 days

期刊介绍： Official journal of the SNFMI, La revue de medecine interne is indexed in the most prestigious databases. It is the most efficient French language journal available for internal medicine specialists who want to expand their knowledge and skills beyond their own discipline. It is also the main French language international medium for French research works. The journal publishes each month editorials, original articles, review articles, short communications, etc. These articles address the fundamental and innumerable facets of internal medicine, spanning all medical specialties. Manuscripts may be submitted in French or in English. La revue de medecine interne also includes additional issues publishing the proceedings of the two annual French meetings of internal medicine (June and December), as well as thematic issues.