Vacuolar myopathies

Chloroquine causes a vacuolar myopathy with the formation of lysosomal complexes. There is conflicting evidence on the selective involvement of particular fiber-types. The myopathy is reversible. 

Muscle biopsy shows vacuolar myopathy of very severe degree affecting all fibers in Pompe s disease but of varying degree and distribution in childhood and adult AMD. In adult AMD, biopsy specimens from unaffected muscles may appear normal by light microscopy. The vacuoles contain PAS-positive material, a marker for glycogen. Electron microscopy shows abundant glycogen, both within membranous sacs, presumably lysosomes, and free in the cytoplasm. 

Muscle biopsy shows severe vacuolar myopathy with glycogen storage. On electron microscopy, the vacuoles correspond to pools of glycogen free in the cytoplasm. 

Yang Z, Vatta M (2007) Danon disease as a cause of autophagic vacuolar myopathy. Congenit Heart Dis 2(6) 404-409... 

Bokuda K, Sugaya K, Tamura S, Miyamoto K, Matsubara S, Komori T. Minocydine-assodated riimned vacuolar myopathy in a patient with rheumatoid arthritis. BMC Neurol 2012 12 140. 

These include the following (a) s-IBM is a vacuolar myopathy with protein aggregates (inclusions), which include aggregates containing amyloid-P, phosphorylated-tau, a-synudein, parkin, and many other AMieimer- and Parkinson-type proteins in those accumnlations (see Chapters 7 and 10). s-IBM still lacks a definitive treatment (see Chapter 7). (b) Hereditary indusion-body myopathy is dne to mutation of the GNE or VCPgene (see Chapters 12 and 15). (c) Adult-onset add-maltase defidency. (d) Dermatomy-ositis often well-treatable (see above and Chapter 3). 

Among several of our patients with other non-IBM vacuolar myopathies, including acid-maltase deficiency, hypokalemic periodic paralysis, myofibrillar myopathy, and undefined types, none had true amyloid deposits as identified by crystal violet staining. Abnormal muscle fibers in myofibrillar myopathy (as originally reported by De Bleecker et al. [9]) indeed have fluorescence-enhanced congophilic accumulations, but we doubt that in... 

Sadeh M, Gadoth M, Hadar H, Ben David E (1993) Vacuolar myopathy sparing the quadriceps. Brain 116, 217-232. 

Corticosteroids a chronic painless myopathy associated with the long-term use of corticosteroids is a particularly common example of drug-induced muscle disorder. It is almost certain that mild cases are overlooked because steroids are so frequently used to treat inflammatory myopathies such as polymyositis. Fluorinated steroids are particularly frequently implicated, and the incidence of drug-induced muscle disease is dose and time-related. The presence of muscle weakness can even complicate topical steroid therapy. Corticosteroid-induced myopathy is mediated via intramuscular cytosolic steroid receptors. The steroid-receptor complexes inhibit protein synthesis and interfere with oxidative phosphorylation. The myopathy is associated with vacuolar changes in muscle, and the accumulation of cytoplasmic glycogen and mitochondrial aggregations. 

Slow-channel syndrome. Abnormally long-lived openings of mutant AChR channels result in prolonged endplate currents and potentials, which in turn elicit one or more repetitive muscle action potentials of lower amplitude that decrement. The morphologic consequences stem from prolonged activation of the AChR channel that causes cationic overload of the postsynaptic region - the endplate myopathy - with Ca2+ accumulation, destruction of the junctional folds, nuclear apoptosis, and vacuolar degeneration of the terminal. Some slow-channel mutations in the transmembrane domain of the AChR render the channel leaky by stabilization of the open state, which is populated even in the absence of ACh. Curiously, some slow-channel mutants can be opened by choline even at the concentrations that are normally present in serum. Quinidine, an open-channel blocker of the AchR, is used for therapy. 

Phosphatidylinositol 3,5-bisphosphate (PI-3,5-P2, 6) is the low abundance, newest member of PIPn family (33). It is involved in mediation of several cellular processes such as vacuolar homeostasis, membrane trafficking, and vesicular protein sorting (36, 38). The recently discovered PI-3,5-P2 effectors include a family of -propeller, epsin, and CHMP protein families (39). The importance of PI-3,5-P2 in human physiology is demonstrated by its role in insulin signaling, myotubular myopathy, and corneal dystrophy (38). 

Ro LS, Lee-Chen GJ, Wu YR et al. (2005) Phenotypic variahihty in a Chinese family with rimmed vacuolar distal myopathy. J Neurol Neurosurg Psychiatry. 76, 752-755. 

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