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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。
Objective To analyze the clinical and mutation detection of LAMP2 gene in Danon children with hypertrophic cardiomyopathy. Methods A 3-year-old male patient (proband) admitted to Pediatrics Department of Peking University First Hospital in October 2013 mainly performed hypertrophic cardiomyopathy and conducted clinical investigation and gene analysis for the definite cause. Results in children (proband) intelligence exercise and physical development normal, admitted to the medical examination found abnormal liver enzymes. Serum alanine aminotransferase, aspartate aminotransferase, creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, hydroxybutyrate dehydrogenase increased. ECG showed left ventricular high voltage, Q-T interval extended. Echocardiography showed ventricular septal and left ventricular wall thickening, left ventricular apex trabecular increased mitral regurgitation, in line with the diagnosis of hypertrophic cardiomyopathy. LAMP2 gene analysis showed that there was a homozygous mutation of c.973-974insC (p.L325fs) in children. Mothers with unexplained hypertrophic cardiomyopathy were heterozygous carriers of c.973-974insC. His father is healthy, LAMP2 gene is normal. c.973-974insC is a newly found mutation that results in a frame shift mutation and produces one codon that prematurely terminates translation. Conclusion Danon’s disease is a rare fatal inherited cardiomyopathy. In this paper, the first Danon’s disease in China was confirmed by genetic testing. LAMP2 gene analysis not only helps diagnose Danon’s disease, which is crucial for guiding pediatric genetic counseling and prenatal diagnosis.