一个法布里病家系报道并文献复习  

Report of a pedigree with Fabry disease and review of literature

作　　者：纪永松[1] 王朝晖[2] 潘晓霞[2] 王展鹏[1] 石智勇[1] 刘洪亮[1] 欧阳彦[2] 杨俪[2] 程瑜[3] 陈楠[2] 

机构地区：[1]河南宏力医院肾脏内科,河南新乡453400 [2]上海交通大学医学院附属瑞金医院肾脏内科,上海200025 [3]上海交通大学医学院附属瑞金医院眼科,上海200025

出　　处：《诊断学理论与实践》2015年第1期51-57,共7页Journal of Diagnostics Concepts & Practice

基　　金：国家重点基础研究发展计划(973计划)(2012CB517604);国家自然科学基金(81170634);上海市科委2011年度科技创新行动计划重大科技项目(11DZ1950307)

摘　　要：目的 :对1个法布里病(Fabry病)患者及其家系进行调查,分析其临床表现、实验室检查、α-半乳糖苷酶A(alpha-galactosidase A,α-Gal A)检测和基因突变,并对照文献复习,以提高医师对法布里病的认识。方法 :对1例法布里病先证者及其家系成员共21人进行家系调查,登记基本资料,同时行血尿常规、血生化、外周血粒细胞α-Gal A活性和基因检测以及眼科、耳听力、头颅MRI、经颅多普勒超声、心电图、超声心动图、肺功能等相关系统检查,α-Gal A活性检测采用底物荧光法,基因检测采用PCR直接测序法。结果 :121例家系成员中检测出11例法布里病患者;2患者的临床表现及辅助检查结果无特异性表现;3外周血粒细胞α-Gal A活性检测结果异常者有6例,GLA基因突变11例;4不同基因突变导致的法布里病患者的临床表现不同;5首次在一个法布里病家系中发现2个不同位点的基因突变,9例突变位于7号外显子(1098del C),2例突变位于4号外显子(596T>C,p.V199A);611例法布里病患者中经典型患者生活质量受影响较大,而迟发型者生活没有任何影响。结论:1法布里病在该家系成员中发生率高(11/21),因此对于法布里病先证者一定要进行家系调查,可早期发现家族中的患者;2法布里病患者的临床和实验室检查均缺乏特异性表现,但该病可累及多个系统,故应加强对临床表现为多系统受累患者的筛查;3α-Gal A活性异常多存在于经典型的法布里病患者中,而迟发型患者该检测结果常正常,因此诊断法布里病的金标准为基因检测,尤其是对于女性杂合子更重要;4法布里病患者因基因突变位点不同而导致临床表现不同;5法布里病父不传子,发现父子同时患病的异常情况时一定要寻找可能的原因,最终明确病因;6经典型法布里病患者的生活质量受影响明显。Objective： To improve the understanding of Fabry disease by pedigree investigation and studying clinical manifestations, laboratory examination, detection of α-galactosidase A（α-Gal A）, analysis of genetic mutation as well as review of literatures. Methods： A proband of Fabry disease and his 21 family members underwent a family line investigation and the basic information was recorded. Urinalysis, blood cell biochemistry, α-Gal A activity in peripheral blood granulocytes, genetic testing, fundus examination, hearing test, skull MRI, transcranial Doppler ultrasound, ECG, echocardiography and pulmonary function tests were performed. α-Gal A activity was detected by substrate fluorescence and gene detection by PCR direct sequencing. Results： Eleven of the 21 family members were diagnosed as having Fabry disease. Results of clinical and laboratory examinations was not specific. α-galactosidase activity in peripheral blood granulocytes was abnormal in 6patients and gene mutations were identified in 11 cases. Patients with different gene mutations had different clinical manifestations. Two different sites of mutation identified in a pedigree of Fabry disease was firstly reported. Mutation was located in the 7th exon（1098del C） in 9 cases, and in 4th exon（596T〉 C, p.V199A） in 2 cases. The quality of life was seriously influenced in patients with classic Fabry disease, and was without any influence in patients with delayed type of disease.Conclusions： Incidence of Fabry disease in this pedigree was 52.38%（11/21）; pedigree investigation should be performed to find the patients. Patients with Fabry disease lack specific clinical and laboratory manifestations, but with involvement of multiple systems, therefore, multi-system screening should be strengthened. Activity of α-Gal A is commonly abnormal in patients with classic type, while in patients with delayed type it is often normal. Gold standard for diagnosis of Fabry disease is genetic test, it is especially important for detection of fema

关 键 词：法布里病 Α-半乳糖苷酶A GLA基因突变 

分 类 号：R596[医药卫生—内科学]