Germain Dominique P, Altarescu Gheona, Barriales-Villa Roberto, Mignani Renzo, Pawlaczyk Krzysztof, Pieruzzi Federico, Terryn Wim, Vujkovac Bojan, Ortiz Alberto
French Referral Center for Fabry disease and MetabERN European Reference Network for Inherited Metabolic Diseases, Division of Medical Genetics, University of Versailles, Paris-Saclay University, 2, allée de la source de la Bièvre, 78180 Montigny, France.
Shaare Zedek Institute of Medical Genetics, Shaare Zedek Medical Center, Shmu'el Bait St 12, Jerusalem 9103102, Israel.
Mol Genet Metab. 2022 Sep-Oct;137(1-2):49-61. doi: 10.1016/j.ymgme.2022.07.010. Epub 2022 Jul 26.
Fabry disease is an X-linked inherited lysosomal disorder that causes accumulation of glycosphingolipids in body fluids and tissues, leading to progressive organ damage and reduced life expectancy. It can affect both males and females and can be classified into classic or later-onset phenotypes. In classic Fabry disease, α-galactosidase A (α-Gal A) activity is absent or severely reduced and disease manifestations have an early onset that can affect multiple organs. In contrast, in later-onset Fabry disease, patients have residual α-Gal A activity and clinical features are primarily confined to the heart. Individualized therapeutic goals in Fabry disease are required due to varying phenotypes and patient characteristics, and the wide spectrum of disease severity. An international group of expert physicians convened to discuss and develop practical clinical recommendations for disease- and organ-specific therapeutic goals in Fabry disease, based on expert consensus and evidence identified through a structured literature review. Biomarkers reflecting involvement of various organs in adult patients with classic Fabry disease are discussed and consensus recommendations for disease- and organ-specific therapeutic goals are provided. These consensus recommendations should support the establishment of individualized approaches to the management of patients with classic Fabry disease by considering identification, diagnosis, and initiation of disease-specific therapies before significant organ involvement, as well as routine monitoring, to reduce morbidity, optimize patient care, and improve patient health-related quality of life.
法布里病是一种X连锁遗传性溶酶体疾病，可导致糖鞘脂在体液和组织中蓄积，进而引起进行性器官损害并缩短预期寿命。该病可影响男性和女性，可分为经典型或迟发型表型。在经典型法布里病中，α-半乳糖苷酶A（α-Gal A）活性缺乏或严重降低，疾病表现较早出现，可累及多个器官。相比之下，在迟发型法布里病中，患者具有残余的α-Gal A活性，临床特征主要局限于心脏。由于表型和患者特征各异，以及疾病严重程度范围广泛，法布里病需要个体化的治疗目标。一个国际专家医师小组召开会议，基于专家共识和通过结构化文献综述确定的证据，讨论并制定法布里病针对疾病和器官的治疗目标的实用临床建议。文中讨论了反映成年经典型法布里病患者各器官受累情况的生物标志物，并提供了针对疾病和器官的治疗目标的共识建议。这些共识建议应支持建立个体化方法来管理经典型法布里病患者，即在重要器官受累之前考虑识别、诊断和启动疾病特异性治疗，以及进行常规监测，以降低发病率、优化患者护理并改善患者的健康相关生活质量。
