法布里病患者临床表现及酶替代治疗的疗效分析  

Clinical features and treatment effect of enzyme replacement therapy in patients with Fabry disease

作　　者：于澈 周艳满 李卓 孙晶 王荣 Yu Che;Zhou Yanman;Li Zhuo;Sun Jing;Wang Rong(Department of Nephrology,Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan 250021,China)

机构地区：[1]山东第一医科大学附属省立医院肾内科,济南250021

出　　处：《中华肾脏病杂志》2022年第6期497-503,共7页Chinese Journal of Nephrology

基　　金：山东省医药卫生科技发展计划(202003051385、202004110804);济南市科技计划(202019124)。

摘　　要：目的分析法布里病(Fabry disease,FD)患者临床表现特点、酶替代治疗疗效及不良反应。方法收集2020年6月至2021年9月山东第一医科大学附属省立医院确诊的FD患者的临床资料,回顾性分析患者的临床表现、实验室检查、基因突变类型、酶替代治疗疗效及不良反应。结果16例FD患者入选本研究,其中经典型12例,迟发型4例,临床表现各异。与迟发型组患者比较,经典型组患者发病年龄较轻(P=0.001),血浆α半乳糖苷酶A(α-Gal A)活性较低(P=0.016);脱乙酰基三己糖酰基鞘脂醇(Lyso-GL-3)水平较高(P=0.030)。经典型组[(13.50±10.08)年]和迟发型组[(10.75±7.27)年]患者延迟诊断时间均较长。7例接受规律酶替代治疗6次的患者血浆Lyso-GL-3水平较治疗前显著下降(P=0.018),5例患者疼痛缓解。3例不规律酶替代治疗患者症状加重;1例患者在规律酶替代治疗期间仍有脑卒中发作。阿加糖酶β和α用药均未发生严重不良反应。结论酶替代治疗可有效降低FD患者血浆Lyso-GL-3水平,缓解临床症状,安全性较好,但疗效具有剂量依赖性,临床获益需要更长时间的观察和随访。酶替代治疗要求患者依从性较好,且能接受长期规律治疗。Objective To analyze the clinical features,efficacy and adverse reactions of enzyme replacement therapy(ERT)in patients with Fabry disease(FD).Methods The clinical data of FD patients in Shandong Provincial Hospital Affiliated to Shandong First Medical University from June 2020 to September 2021 were collected and the clinical manifestations,laboratory examinations,gene mutations,and efficacy and adverse reactions of ERT were retrospectively analyzed.Results Sixteen patients with FD were enrolled in this study,including 12 typical cases and 4 late-onset cases,with varied clinical manifestations.Compared with late-onset patients,typical patients had younger age of onset(P=0.001),lower activity of plasma alpha-galactosidase A(P=0.016)and higher globotriaosylsphingosine(lyso-GL-3,P=0.030).The typical patients[(13.50±10.08)years]and late-onset patients[(10.75±7.27)years]both had long delayed time of diagnosis.In 7 patients who underwent regular 6 ERT,lyso-GL-3 was significantly lower than before(P=0.018);after 6 treatments,the pain of 5 patients was relieved than before.Three patients with irregular ERT had aggravated symptoms,and 1 case had stroke recurrence during regular treatment.No serious adverse reaction occurred with the use of agalsidaseβandα.Conclusions ERT can effectively reduce the level of plasma lyso-GL-3 in patients with FD and relieve symptoms,and has good safety.But the efficacy of ERT is dose-dependent,and clinical benefits require long-term observation and follow-up.Patients treated with ERT should have good compliance and can receive long-term regular treatment.

关 键 词：法布里病 酶替代疗法 治疗结果 临床表现 脱乙酰基三己糖酰基鞘脂醇 

分 类 号：R692[医药卫生—泌尿科学]