Clinical features, genetic variations and enzyme replacement therapy in five Chinese patients with Fabry disease
10.3760/cma.j.cn441217-20211210-00097
- VernacularTitle:5例法布里病患者临床表现、基因变异及酶替代疗法效果分析
- Author:
Wenqing CHEN
1
;
Heng LI
;
Lifang ZHI
;
Jiong TIAN
;
Yan JIANG
;
Huijuan YE
;
Jianghua CHEN
Author Information
1. 浙江大学医学院附属第一医院肾脏病中心 浙江省肾脏病防治技术研究重点实验室 国家临床重点专科 浙江大学肾脏病研究所 浙江省肾脏与泌尿系统疾病临床医学研究中心，杭州 310003
- Keywords:
Fabry disease;
Gene variation;
Enzyme replacement therapy;
Clinical features;
Adverse events
- From:
Chinese Journal of Nephrology
2022;38(8):678-684
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the efficacy and safety of enzyme replacement therapy (ERT) in Chinese patients with Fabry disease.Methods:A retrospective analysis of the clinical manifestations, genetic variations, family screening, treatments and adverse reactions was conducted in five patients with Fabry disease admitted to the First Affiliated Hospital of Zhejiang University College of Medicine from July 2020 to May 2021. The dosage of agalsidase β was 1 mg/kg by intravenous pump once every 2 weeks.Results:Five male patients with median age of 37 years old (29-51 years old) were diagnosed based on clinical features, family history, α-galactosidase A (α-Gal A) activity, genetic analysis results and kidney biopsy. The clinical manifestations varied in these five patients. All patients had abnormal electrocardiogram, abnormal cardiac ultrasonography and abnormal urinalysis results, three experienced acroparaesthesia during childhood (one patient had persistent pain until adulthood), three had cutaneous angiokeratoma, four had renal insufficiency, four had hypohidrosis, four had diarrheas, four had cornea verticillata and two had high-frequency hearing loss. Two missense mutations of the GLA gene were identified: c.272T>C(p.I91T) and c.868A>G(p.Met290Val). Two nonsense mutations were c.1024C>T(p.Arg342*) and c.838C>T(p.Gln280*). Furthermore, the frameshift mutation c.348del p.(Ile117Phefs*4) was detected, which was not included in the known database, presented with classical Fabry disease. There was no serious adverse reaction during agalsidase β infusion in 5 patients. ERT reduced the plasma globotriaosylsphingosine (lyso-GL-3) levels after treatment of 2-10 months ( P<0.05), and the long-term diarrhea symptom were significantly improved. Conclusions:The clinical manifestations of Fabry disease are varied. Severe adverse events rarely occur in patients treated with short-term ERT. Plasma lyso-GL-3 levels decrease significantly after treatment.
