Ⅳ型糖原累积病5例临床和基因分析  

The clinical and genetic analysis of glycogen storage disease type Ⅳ in 5 cases

作　　者：房迪[1] 邱文娟[1] 叶军[1] 韩连书[1] 张惠文[1] 余永国[1] 梁黎黎[1] 龚珠文[1] 闫慧[1] 王建国 顾学范[1] FANG Di;QIU Wenjuan;YE Jun;HAN Lianshu;ZHANG Huiwen;YU Yongguo;LIANG Lili;GONG Zhuwen;YAN Hui;WANG Jianguo;GU Xuefan(Department of Pediatric Endocrinology/Genetics, Shanghai Institute of Pediatric Research, Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China)

机构地区：[1]上海交通大学医学院附属新华医院,上海儿科医学研究所内分泌/遗传科,上海200092

出　　处：《临床儿科杂志》2018年第3期216-220,共5页Journal of Clinical Pediatrics

基　　金：国家自然科学基金(No.81170811,30793216);国家重点研发计划精准医学研究专项(No.2016YFC0905100);上海市卫生和计划生育委员会基金(No.20134005)

摘　　要：目的探讨糖原累积病Ⅳ型(GSD Ⅳ)的临床、实验室检查及基因突变特点。方法分析5例GSD Ⅳ患儿的临床表现、生化指标、壳三糖酶活性及治疗随访情况。结果患儿男3例、女2例,于4个月~5岁2个月因肝脾肿大及肝功能异常就诊。2例伴运动发育落后和肌无力,但肌酸激酶水平正常;4例肝脏活检示肝糖原沉积和不同程度肝纤维化。靶向测序发现5例患儿均携带GBE1基因复合杂合突变,共发现2种已报道突变(p.R515C,p.R524Q)和7种新突变,新突变包含5种错义突变(p.I460T、p.F76S、p.F538V、p.L650R、p.W455R),1种插入突变(c.141_142ins GCGC)及1种大片段缺失(外显子3-7),确诊为肝型GSD Ⅳ型。2例因肝硬化死亡;1例因肝硬化行亲体肝移植,移植前血壳三糖酶活性显著升高而移植后明显下降,移植后4个月肝酶恢复正常;另2例生长发育和肝功能基本正常,1例未行特殊治疗,1例服用生玉米淀粉,其血壳三糖酶活性正常。结论 GSD Ⅳ的临床表现异质性大,靶向测序可快速明确诊断,壳三糖酶有助于判断预后。Objective To investigate the characteristics of glycogen storage disease type IV(GSD IV)clinically,in laboratory tests and in gene mutation.Methods The clinical manifestations,biochemical indexes,activity of chitotriosidase,and the follow-up of the treatment in5cases of GSD IV were analyzed.Results Five patients(3boys and2girls)aged4months-5years presented hepatosplenomegaly and elevated liver enzyme levels for2months at hospital visit.Two patients had motor developmental delay and weakness but their creatine kinase(CK)level were normal.Glycogen storage and liver fibrosis were observed in the liver biopsy in4patients.Target sequencing found that all5children carried the complex heterozygous mutation of the GBE1gene with2reported mutations(p.R515C,p.R524Q)and7novel mutations.The novel mutation contains5missense mutations(p.I460T,p.F76S,p.F538V,p.L650R,p.W455R),one insertion mutations(c.141_142insGCGC),and one large fragment deletion(exon3-7).Therefore,diagnosis of liver type of GSD IV was confirmed in those children.Two patients died of liver cirrhosis.The liver transplantation was performed due to liver cirrhosis in one patient whose chitotriosidase activity increased obviously before transplantation and decreased significantly after the transplantation and liver enzyme levels were returned to normal4months after transplantation.In the other two patients their growth and liver enzyme levels were normal;one had not received special treatments while the other was treated with raw corn starch and level of chitotriosidase was normal.Conclusions The clinical manifestations of GSD IV are heterogeneous.Target sequencing can be used for fast and noninvasive diagnosis of GSD IV.Chitotriosidase activity is useful in the prognosis assessment for GSD IV.

关 键 词：糖原累积病Ⅳ型 GBE1基因 靶向测序 壳三糖酶 

分 类 号：R725.9[医药卫生—儿科]