Autophagic vacuoles with sarcolemmal features delineate Danon disease and related myopathies.
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.
Sugie
Kazuma
K
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.
Noguchi
Satoru
S
Kozuka
Yoshimichi
Y
Arikawa-Hirasawa
Eri
E
Tanaka
Mikihito
M
Yan
Chuanzhu
C
Saftig
Paul
P
von Figura
Kurt
K
Hirano
Michio
M
Ueno
Satoshi
S
Nonaka
Ikuya
I
Nishino
Ichizo
I
D000110:Acetylcholinesterase / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D001343:Autophagy / Q000502:physiology*; D002038:Bungarotoxins / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007223:Infant; D051907:Lysosomal Membrane Proteins; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron / Q000379:methods; D008954:Models, Biological; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009135:Muscular Diseases / Q000145:classification / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D012508:Sarcolemma / Q000378:metabolism / Q000473:pathology*; D014617:Vacuoles / Q000378:metabolism / Q000648:ultrastructure
D015703:Antigens, CD; D002038:Bungarotoxins; D006023:Glycoproteins; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D000110:Acetylcholinesterase