Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
J Hum Genet. 2012 Jul;57(7):407-10. doi: 10.1038/jhg.2012.72. Epub 2012 Jun 14.
Danon disease is a rare X-linked dominant lysosomal disease due to the primary deficiency of lysosome-associated membrane protein 2 (LAMP2) gene. Cardiomyopathy, skeletal myopathy and mental retardation are the typical triad of Danon disease. More than 60 LAMP2 mutations have been reported. The molecular mechanism is defects in LAMP2 protein (due to LAMP2 mutation) which causes insidious glycogen accumulation in cardiac muscle cells and resulting in cardiac hypertrophy and electrophysiological abnormalities. However, there are significant differences between the male and female Danon disease patients with regard to clinical features and cardiac manifestations. The clinical symptoms are variable, from asymptomatic to sudden cardiac death. Wolff-Parkinson-White syndrome is more common in male than female patients. Hypertrophic cardiomyopathy is predominant in male patients, whereas the similar prevalence of hypertrophic and dilated cardiomyopathy in female patients. Male patients are diagnosed usually at teenage, whereas the diagnosis and events occurred approximately 15 years later in female than male patients. Heart transplantation is the reliable treatment once the occurrence of heart failure and should be considered as early as possible due to its rapid progression.
丹农病是一种罕见的 X 连锁显性溶酶体疾病，主要由于溶酶体相关膜蛋白 2 （LAMP2）基因的原发性缺乏所致。心肌病、骨骼肌病和智力迟钝是丹农病的典型三联征。已经报道了超过 60 种 LAMP2 突变。分子机制是 LAMP2 蛋白（由于 LAMP2 突变）的缺陷导致心肌细胞中糖原的逐渐积累，从而导致心肌肥厚和电生理异常。然而，男性和女性丹农病患者在临床特征和心脏表现方面存在显著差异。临床症状多种多样，从无症状到心脏性猝死。男性患者比女性患者更常见沃夫-帕金森-怀特综合征。男性患者以肥厚型心肌病为主，而女性患者肥厚型和扩张型心肌病的患病率相似。男性患者通常在青少年期被诊断出，而女性患者的诊断和发病时间比男性患者晚约 15 年。一旦发生心力衰竭，心脏移植是可靠的治疗方法，由于其进展迅速，应尽早考虑。
