Danon病心内膜心肌活检病理诊断

Pathological diagnosis of Danon disease by endomyocardial biopsy

目的探讨Danon病的临床病理学特征及鉴别诊断要点。方法收集2019年1—12月首都医科大学附属北京安贞医院确诊的2例Danon病患者资料,行HE染色、免疫组织化学标记、电镜检查及基因检测。结果患者均为男性,年龄分别为21岁和19岁,2例患者临床均表现为肥厚型心肌病。心内膜心肌活检镜下组织学特征为心肌细胞肥大,细胞空泡样变性,心肌细胞中央可见窗格状透明区域,细胞核增大、深染、畸形,部分心肌细胞内可见脂褐素。超微结构特征性表现为糖原聚集。基因检测结果分别为:LAPM2基因移码突变(c.973delC)和半合子插入突变(c.719721dupAGC)。结论Danon病是一种罕见的LAMP2基因突变导致的疾病,以肥厚型心肌病为典型临床表现。心肌细胞空泡变性是典型组织学特征,心肌细胞内糖原颗粒异常聚积为超微结构特征,结合LAMP2基因突变即可确诊Danon病;熟悉该病的临床病理学特征可避免漏诊。

Objective To investigate the clinicopathological features and differential diagnosis of Danon disease.Methods Two cases of Danon disease were selected from Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2019 to December 2019.The clinical history,histological,immunohistochemical,ultrastructural and gene mutation analysis were collected.Results Both of the patients were male,aged 21 and 19 years old,respectively.They were diagnosed with hypertrophic cardiomyopathy by clinicians.The histologic features of endocardial biopsies were hypertrophy and vacuolar degeneration of cardiomyocytes.Part of cardiomyocytes appeared as intracellular clear areas lacking myofibers.The nuclei were large,irregular and hyperchromatic.And lipofuscin was occasionally observed in the nuclei of cardiomyocytes.Ultrastructural feature of electron microscopic was glycogen accumulation.Genetic analysis identified two lysosome-associated membrane protein-2(LAMP2)gene mutations.A 1-bp deletion in exon 8(c.973delC)was found in patient 1,leading to a frame-shift mutation.A 3-bp duplication in exon 5(c.719_721dupAGC)was found in patient 2,leading to an insertion mutation.Conclusions Danon disease is a rare disease characterized by hypertrophic cardiomyopathy.It is caused by mutations in the LAMP2 gene.Vacuolar degeneration of cardiomyocytes,glycogen accumulation under electron microscope and the mutation of LAMP2 gene are the critical features of Danon disease.Familiar with its clinicopathological characteristics would be helpful to avoid the misdiagnosis of Danon disease.