Abstract
Three unrelated patients, one girl, one boy, and an adult female, aged 14, 11 and 41 years, respectively, at the time of biopsy, revealed lysosomal glycogen storage, autophagic vacuoles and peculiar globular inclusions of distinct ultrastructure, which were reducing but did not appear like true “reducing bodies” as described in the congenital myopathy “reducing body myopathy”. All three patients had residual activity of acid α-glucosidase in their muscle biopsy samples. Leukocytes in the girl showed normal acid α-glucosidase activity, but in the boy activity was reduced. Molecular genetic analysis of the GAA gene revealed disease-causing mutations in each patient: H568L/R672W, IVS1–13T>G/G615F, and IVS1–13T>G/IVS1–13T>G. Although only one patient with such globular inclusions has been reported up to now, the three patients described here indicate that in the late-onset type of GSD II such inclusions may not be rare.
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Angelini C, Cenacchi G, Nascimbeni AC, Fulizio L (2003) Morphological changes in late onset acid maltase deficiency patients with splicing gene mutation. Acta Myol 22:90−96
Bertini E, Salviati G, Apollo F, Ricci E, Servidei S, Broccolini A, Papacci M, Tonali P (1994) Reducing body myopathy and desmin storage in skeletal muscle: morphological and biochemical findings. Acta Neuropathol 87:106−112
Boerkoel CF, Exelbert R, Nicastri C, Nichols RC, Miller FW, Plotz PH, Raben N (1995) Leaky splicing mutation in the acid maltase gene is associated with delayed onset of glycogenosis type II. Am J Hum Genet 56:887−897
Brooke MH, Neville HE (1972) Reducing body myopathy. Neurology 22:829−840
Fernandez-Hojas R, Huie ML, Navarro C, Dominguez C, Roig M, Lopez-Coronas D, Teijeira S, Anyane-Yeboa K, Hirschhorn R (2002) Identification of six novel mutations in the acid alpha-glucosidase gene in three Spanish patients with infantile onset glycogen storage disease type II (Pompe disease). Neuromuscul Disord 12:159−166
Goebel HH, Borchert A (2002) Protein surplus myopathies and other rare congenital myopathies. Semin Pediatr Neurol 9:160−170
Goebel HH, Shin YS, Gullotta F, Yokota T, Alroy J, Voit T, Haller P, Schulz A (1992) Adult polyglucosan body myopathy. J Neuropathol Exp Neurol 51:24−35
Goebel HH, Halbig LE, Goldfarb L, Schober R, Albani M, Neuen-Jacob E, Voit T (2001) Reducing body myopathy with cytoplasmic bodies and rigid spine syndrome: a mixed congenital myopathy. Neuropediatrics 32:196−205
Hagemans MLC, Winkel LPF, Van Doorn PA, Hop WH, Loonen MCB, Reuser AJJ, Van der Ploeg AT (2005) Clinical manifestation and natural course of late-onset Pompe’s disease in 54 Dutch patients. Brain 128:671−677
Hermans MM, Leenen D van, Kroos MA, Beesley CE, Van Der Ploeg AT, Sakurba H, Wevers R, Kleijer W, Michelakakis H, Kirk EP, et al (2004) Twenty-two novel mutations in lysosomal α-glucosidase gene (GAA) underscores the genotype-phenotype correlation in glycogen storage disease type II. Hum Mutat 23:47−56
Hirschhorn R, Reuser AJJ (2001) Glycogen storage disease type II: acid α-glucosidase (acid maltase) deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 3389−3420
Hübner G, Pongratz D (1982) Granularkörpermyopathie (sog. reducing body myopathy). Pathologe 3:111−113
Huie ML, Chen AS, Tsujino S, Shanake S, DiMauro S, Engel AG, Hirschhorn R (1994) Aberrant splicing in adult onset glycogen storage disease type II (GSDII): molecular identification of an IVS1(-13T>G) mutation in a majority of patients and a novel IVS10(+1GT>CT) mutation. Hum Mol Genet 3:2231−2236
Iancu TC, Lerner A, Shiloh H, Bashan N, Moses S (1988) Juvenile acid maltase deficiency presenting as paravertebral pseudotumour. Eur J Pediatr 147:372−376
Jay V, Christodoulou J, Mercer-Connolly A, McInnes RR (1992) “Reducing body”-like inclusions in skeletal muscle in childhood-onset acid maltase deficiency. Acta Neuropathol 85:111−115
Kiyomoto BH, Murakami N, Kishibayashi J, Sunohara N, Nonaka I (1995) Reducing bodies in distal myopathy with rimmed vacuole formation. Acta Neuropathol 89:109−111
Kiyomoto BH, Murakami N, Kobayashi Y, Nihei K, Tanaka T, Takeshita K, Nonaka I (1995) Fatal reducing body myopathy: ultrastructural and immunohistochemical observations. J Neurol Sci 128:58−65
Kroos MA, Van der Kraan M, Van den Boogaard MJ, Ausems MGEM, Ploos van Amstel HK, Poenaru L, Nicolino M, Wevers RA, Diggelen OP van, Kleijer WJ, Reuser AJJ (1995) Glycogen storage disease type II: the frequency of three common mutant alleles and their associated clinical phenotypes studied in 121 patients. J Med Genet 32:836−837
Lafôret P, Nicolino M, Eymard B, Puech JP, Caillaud C, Poenaru L, Fardeau M (2000) Juvenile and adult-onset acid maltase deficiency in France: genotype-phenotype correlation. Neurology 55:1122−1128
Minato S, Kobayashi T, Tanaka K, Kitaguchi T, Goto I (1988) Adult Pompe disease with normal acid α-glucosidase activity in leukocytes (in Japanese). Rinsho Shinkeigaku 28:413−416
Neudecker S, Krasnianski M, Bahn E, Zierz S (2004) Rimmed vacuoles in facioscapulohumeral muscular dystrophy: a unique ultrastructural feature. Acta Neuropathol 108:257−259
Radojevic V, Humm AM, Rösler KM, Lauterburg T, Burgunder J-M (2003) Abnormal trafficking of sarcolemmal proteins in α-glucosidase deficiency. Acta Neuropathol 105:373−380
Shin YS (1990) Diagnosis of glycogen storage disease. J Inherit Metab Dis 13:419−434
Thiéry JP (1967) Mise en evidence des polysaccharides sur coupes fines en microscopie electronique. J Microsc 6:987−1018
Acknowledgements
We gratefully acknowledge a fellowship to Dr. M.C. Sharma from the Deutsche Forschungsgemeinschaft (DFG−INSA), the technical support of Ms. M. Schlie and Ms. I. Warlo, photographic assistance from Mr. W. Wagner and editorial help of Ms. A. Wöber.
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After this paper went to print, both parents of patient 3 were found to be heterozygous for a IVS1-13t>g mutation in intron 1 of the GAA gene for GSD II.
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Sharma, M.C., Schultze, C., von Moers, A. et al. Delayed or late-onset type II glycogenosis with globular inclusions. Acta Neuropathol 110, 151–157 (2005). https://doi.org/10.1007/s00401-005-1026-4
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DOI: https://doi.org/10.1007/s00401-005-1026-4