Abstract
Histochemical and electron microscopic studies were performed in an attempt to clarify the muscle pathology in an 18-year-old man with Fabry disease, showing proximal limb muscle atrophy, and his 52-year-old mother, who is a Fabry carrier with hypertrophic cardiomyopathy. Despite the relatively mild myopathic changes revealed by histochemistry, electron microscopy demonstrated the widespread accumulation of abundant lamellated bodies in myofibers, associated with increased glycogen granules and autophagic vacuoles. The cardiac muscle of the proband's mother revealed a mosaic pattern of normal-appearing and hypertrophic myofibers containing a number of ring-like, lamellated bodies. Although further studies are necessary to support our findings, skeletal muscle is apparently involved in patients with Fabry disease, and a mosaic pattern of cardiac muscle involvement possibly reflecting Lyonization, may be one of the characteristic findings of a Fabry disease carrier.
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References
Arahata K, Hoffman EP, Kunkel LM, Ishiura S, Tsukahara T, Ishihara T, Sunohara N, Nonaka I, Ozawa E, Sugita H (1989) Dystrophin diagnosis: comparison of dystrophin abnormalities by immunofluorescence and immunoblot analyses. Proc Natl Acad Sci USA 86: 7154–7158
Arahata K, Ishihara T, Kamakura K, Tsukahara T, Ishiura S, Baba C, Matsumoto T, Nonaka I, Sugita H (1989) Dystrophin and Duchenne muscular dystrophy. N Engl J Med 321: 398–399
Davies JP, Winchester BG, Malcolm S (1993) Sequence variations in the first exon of α-galactosidase A. J Med Genet 30: 658–663
Desnick RJ, Bishop DF (1989) Fabry disease: α-galactosidase deficiency; Schindler disease: α-N-acetylgalactosaminidase deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York, pp 2905–2947
Eng CM, Resnick-Silverman LA, Niehaus DJ, Astrin KH, Desnick RJ (1993) Nature and frequency of mutations in the α-galactosidase A gene that causes Fabry disease. Am J Hum Genet 53: 1186–1197
Fisher EA, Desnick RJ, Gordon RE, Eng CM, Griepp R, Goldman ME (1992) Fabry disease: an unusual cause of severe coronary disease in a young man. Ann Intern Med 117: 221–223
Hoffman EP, Arahata K, Minetti C et al (1992) Dystrophinopathy in isolated cases of myopathy in females. Neurology 42: 967–975
Ishii S, Sakuraba H, Shimmoto M, Minamikawa-Tachino R, Suzuki T, Suzuki Y (1991) Fabry disease: detection of 13-bp deletion in α-galactosidase A gene and its application to gene diagnosis of heterozygotes. Ann Neurol 29: 560–564
Ishii S, Sakuraba H, Suzuki Y (1992) Point mutations in the upstream region of the α-galactosidase A gene exon 6 in an atypical variant of Fabry disease. Hum Genet 89: 29–32
Ishii S, Kase R, Sakuraba H, Suzuki Y (1993) Characterization of a mutant α-galactosidase gene product for the late-onset cardiac form of Fabry disease. Biochem Biophys Res Commun 197: 1585–1589
Kobayashi T, Shinnoh N, Kuroiwa Y (1984) Metabolism of ceramide trihexoside in cultured skin fibroblasts from Fabry's patients, carriers and normal controls. J Neurol Sci 65: 169–177
Kocen RS, Thomas PK (1970) Peripheral nerve involvement in Fabry's disease. Arch Neurol 22: 81–88
Kumamoto T, Fukuhara N, Nagashima M, Kanda T, Wakabayashi M (1982) Distal myopathy. Histochemical and ultrastructural studies. Arch Neurol 39: 367–371
Lindberg C, Borg K, Edström L, Hedström A, Oldfors A (1991) Inclusion body myositis and Welander distal myopathy: a clinical neurophysiological and morphological comparison. J Neurol Sci 103: 76–81
Lyon MF (1961) Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 190: 372–373
Mastaglia FL, Papadimitrtiou JM, Dawkins RL, Beveridge B (1977) Vacuolar myopathy associated with chloroquine, lupus erythematosus and thymoma. J Neurol Sci 34: 315–328
Matsuishi T, Yoshino M, Terasawa K, Nonaka I (1984) Childhood and maltase deficiency: a clinical, biochemical, and morphologic study of three patients. Arch Neurol 41: 47–52
Ohnishi A, Dyck PJ, Minn R (1974) Loss of small peripheral sensory neurons in Fabry disease. Arch Neurol 31: 120–127
Pellissier JF, Van Hoof F, Bourdet-Bonerandi D, Monier-Faugere MC, Toga M (1981) Morphological and biochemical changes in muscle and peripheral nerve in Fabry's disease. Muscle Nerve 4: 381–387
Schröder JM, Adams RD (1968) The ultrastructural morphology of the muscle fiber in myotonic dystrophy. Acta Neuropathol (Berl). 10: 218–241
Shibasaki H, Tabira T, Inoue N, Goto I, Kuroiwa Y (1973) Carbamazepine for painful crises in Fabry disease. J Neurol Sci 18: 47–51
Sima AAF, Robertson DM (1978) Involvement of peripheral nerve and muscle in Fabry's disease. Histologic, ultrastructural, and morphometric studies. Arch Neurol 35: 291–301
Tachi N, Sasaki K, Yamada T, Imamura S, Miike T (1990) Mosaic pattern of dystrophins in Duchenne muscular dystrophy. Pediatr Neurol 6: 54–56
Tome FMS, Faradeau M, Lenoir G (1977) Ultrastructure of muscle and sensory nerve in Fabry's disease. Acta Neuropathol (Berl) 38: 187–194
Uchino M, Uyama E, Hirano T, Nakamura T, Fukushima T, Ando M (1993) A histochemical and electron microscopic study of skeletal muscle in an adult case of Chediak-Higashi syndrome. Acta Neuropathol 86: 521–524
Veber GA de, Schwarting GA, Kolodny EH, Kowall NW (1992) Fabry disease: immunocytochemical characterization of neuronal involvement. Ann Neurol 31: 409–415
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Uchino, M., Uyama, E., Kawano, H. et al. A histochemical and electron microscopic study of skeletal and cardiac muscle from a Fabry disease patient and carrier. Acta Neuropathol 90, 334–338 (1995). https://doi.org/10.1007/BF00296520
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DOI: https://doi.org/10.1007/BF00296520