Abstract:

Abstracts： Objectives To investigate the clinical features and LAMP2 gene mutation a case with hypertrophic cardiomyopathy due to Danon disease. Methods A boy (proband) of hypertrophic cardiomyopathy due to Danon disease was hospitalized in the Department of Pediatrics of Peking University First Hospital on October, 2013. He was the first child of non-consanguineous Chinese couples. Gene analysis was performed by direct sequencing. Results The patient had not any symptoms with normal intelligence and physical development. Elevated serum alanine aminotransferase had been noticed in a medical examination for entry to kindergarten. His serum alanine aminotransferase, glutamic-oxaloacetic transaminase, creatine phosphokinase, creatine kinase-MB, lactate dehydrogenase, and hydroxybutyrate dehydrogenase were elevated. Electrocardiograph showed left ventricular high voltage, prolonged Q-T interval. Ultrasonic cardiogram showed ventricular septum and left ventricular wall thickening, left ventricular enlargement, increased trabecular of left ventricular apex, and mitral inadequacy, supporting the diagnosis of hypertrophic cardiomyopathy. A homozygous mutation, c.973-974insC (p.L325fs) was detected on LAMP2 gene of the patient. His mother had unexplained hypertrophic cardiomyopathy. She carries a heterozygous mutation c.973-974insC. His father is healthy without any mutation on LAMP2. c.973-974insC was a novel mutation, leading to frameshift mutation and a premature termination codon. Conclusions Danon disease is a rare fatal genetic cardiomyopathy without effective treatment. In this study, a Chinese boy and his mother with Danon disease were firstly diagnosed by gene analysis. LAMP2 gene study is important for the diagnosis of Danon disease and genetic counseling of the family.

Key words: lysosome disease, Danon disease, LAMP2 gene, hypertrophic cardiomyopathy

摘要：

目的 分析以肥厚性心肌病为主要表现的Danon病患儿临床及LAMP2基因突变检测结果。方法 2013年10月北京大学第一医院儿科收治的1例3岁男性儿童（先证者），以肥厚性心肌病为主要表现，为明确病因进行了临床调查及基因分析。结果 患儿（先证者）智力运动及体格发育正常，入托体检发现肝酶异常。血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、肌酸激酶、肌酸激酶同工酶、乳酸脱氢酶、羟丁酸脱氢酶升高。心电图显示左室高电压，Q-T间期延长。超声心动图显示室间隔及左室壁增厚，左室心尖部肌小梁增多，二尖瓣关闭不全，符合肥厚性心肌病诊断。LAMP2基因分析显示：患儿存在c.973-974insC（p.L325fs）纯合突变。母亲患不明原因的肥厚性心肌病，为c.973-974insC杂合突变携带者。其父亲健康，LAMP2基因正常。c.973-974insC为新发现突变，导致框移突变，并产生1个提前终止翻译的密码子。结论 Danon病是一种少见的致死性遗传性心肌病，本文通过基因检测确诊了中国首例Danon病患者。LAMP2基因分析不仅有助于诊断Danon病，对于指导家系遗传咨询及产前诊断至关重要。

关键词: 溶酶体病, Danon病, LAMP2基因, 肥厚性心肌病