Sugie Kazuma, Noguchi Satoru, Kozuka Yoshimichi, Arikawa-Hirasawa Eri, Tanaka Mikihito, Yan Chuanzhu, Saftig Paul, von Figura Kurt, Hirano Michio, Ueno Satoshi, Nonaka Ikuya, Nishino Ichizo
Department of Neuromuscular Research, National Institute of Neuroscience, National Hospital for Mental Nervous and Muscular Disorders, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
J Neuropathol Exp Neurol. 2005 Jun;64(6):513-22. doi: 10.1093/jnen/64.6.513.
Among the autophagic vacuolar myopathies (AVMs), a subgroup is characterized pathologically by unusual autophagic vacuoles with sarcolemmal features (AVSF) and includes Danon disease and X-linked myopathy with excessive autophagy. The diagnostic importance and detailed morphologic features of AVSF in different AVMs have not been well established, and the mechanism of AVSF formation is not known. To address these issues, we have performed detailed histologic studies of myopathies with AVSF and other AVMs. In Danon disease and related AVMs, at the light microscopic level, autophagic vacuoles appeared to be accumulations of lysosomes, which, by electron microscopy consisted of clusters of autophagic vacuoles, indicative of autolysosomes. Some autolysosomes were surrounded by membranes with sarcolemmal proteins, acetylcholinesterase activity, and basal lamina. In Danon disease, the number of fibers with AVSF increased linearly with age while the number with autolysosomal accumulations decreased slightly, suggesting that AVSF are produced secondarily in response to autolysosomes. Most of the AVSF form enclosed spaces, indicating that the vacuolar membranes may be formed in situ rather than through sarcolemmal indentation. This unique intracytoplasmic membrane structure was not found in other AVMs. In conclusion, AVSF with acetylcholinesterase activity are autolysosomes surrounded by secondarily generated intracytoplasmic sarcolemma-like structure and delineates a subgroup of AVMs.
在自噬性空泡性肌病（AVM）中，有一个亚组在病理上的特征是具有肌膜特征的异常自噬空泡（AVSF），包括丹农病和伴有过度自噬的X连锁肌病。AVSF在不同AVM中的诊断重要性和详细形态学特征尚未完全明确，其形成机制也不清楚。为了解决这些问题，我们对伴有AVSF的肌病和其他AVM进行了详细的组织学研究。在丹农病及相关AVM中，在光学显微镜水平，自噬空泡似乎是溶酶体的聚集物，通过电子显微镜观察，其由自噬空泡簇组成，提示为自噬溶酶体。一些自噬溶酶体被含有肌膜蛋白、乙酰胆碱酯酶活性和基底膜的膜所包围。在丹农病中，具有AVSF的纤维数量随年龄呈线性增加，而具有自噬溶酶体聚集的纤维数量略有减少，这表明AVSF是对自噬溶酶体的继发性反应产物。大多数AVSF形成封闭空间，这表明空泡膜可能是原位形成的，而不是通过肌膜凹陷形成。这种独特的胞质内膜结构在其他AVM中未发现。总之，具有乙酰胆碱酯酶活性的AVSF是被继发性产生的胞质内肌膜样结构所包围的自噬溶酶体，它界定了一个AVM亚组。
