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Congenital type IV glycogenosis: the spectrum of pleomorphic polyglucosan bodies in muscle, nerve, and spinal cord with two novel mutations in the GBE1 gene.
Acta Neuropathol. 2008 Nov; 116(5):491-506.AN

Abstract

A diagnosis of GSD-IV was established in three premature, floppy infants based on characteristic, however unusually pleomorphic polyglucosan bodies at the electron microscopic level, glycogen branching enzyme deficiency in two cases, and the identification of GBE1 mutations in two cases. Pleomorphic polyglucosan bodies in muscle fibers and macrophages, and less severe in Schwann cells and microglial cells were noted. Most of the inclusions were granular and membrane-bound; others had an irregular contour, were more electron dense and were not membrane bound, or homogenous ('hyaline'). A paracrystalline pattern of granules was repeatedly noted showing a periodicity of about 10 nm with an angle of about 60 degrees or 120 degrees at sites of changing linear orientation. Malteser crosses were noted under polarized light in the larger inclusions. Some inclusions were PAS positive and others were not. Severely atrophic muscle fibers without inclusions, but with depletion of myofibrils in the plane of section studied indicated the devastating myopathic nature of the disease. Schwann cells and peripheral axons were less severely affected as was the spinal cord. Two novel protein-truncating mutations (c.1077insT, p.V359fsX16; g.101517_127067del25550insCAGTACTAA, DelExon4-7) were identified in these families. The present findings extend previous studies indicating that truncating GBE1 mutations cause a spectrum of severe diseases ranging from generalized intrauterine hydrops to fatal perinatal hypotonia and fatal cardiomyopathy in the first months of life.

Authors+Show Affiliations

Department of Neuropathology, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18661138

Citation

Nolte, Kay W., et al. "Congenital Type IV Glycogenosis: the Spectrum of Pleomorphic Polyglucosan Bodies in Muscle, Nerve, and Spinal Cord With Two Novel Mutations in the GBE1 Gene." Acta Neuropathologica, vol. 116, no. 5, 2008, pp. 491-506.
Nolte KW, Janecke AR, Vorgerd M, et al. Congenital type IV glycogenosis: the spectrum of pleomorphic polyglucosan bodies in muscle, nerve, and spinal cord with two novel mutations in the GBE1 gene. Acta Neuropathol. 2008;116(5):491-506.
Nolte, K. W., Janecke, A. R., Vorgerd, M., Weis, J., & Schröder, J. M. (2008). Congenital type IV glycogenosis: the spectrum of pleomorphic polyglucosan bodies in muscle, nerve, and spinal cord with two novel mutations in the GBE1 gene. Acta Neuropathologica, 116(5), 491-506. https://doi.org/10.1007/s00401-008-0417-8
Nolte KW, et al. Congenital Type IV Glycogenosis: the Spectrum of Pleomorphic Polyglucosan Bodies in Muscle, Nerve, and Spinal Cord With Two Novel Mutations in the GBE1 Gene. Acta Neuropathol. 2008;116(5):491-506. PubMed PMID: 18661138.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Congenital type IV glycogenosis: the spectrum of pleomorphic polyglucosan bodies in muscle, nerve, and spinal cord with two novel mutations in the GBE1 gene. AU - Nolte,Kay W, AU - Janecke,Andreas R, AU - Vorgerd,Matthias, AU - Weis,Joachim, AU - Schröder,J Michael, Y1 - 2008/07/26/ PY - 2008/06/08/received PY - 2008/07/19/accepted PY - 2008/07/14/revised PY - 2008/7/29/pubmed PY - 2008/12/17/medline PY - 2008/7/29/entrez SP - 491 EP - 506 JF - Acta neuropathologica JO - Acta Neuropathol VL - 116 IS - 5 N2 - A diagnosis of GSD-IV was established in three premature, floppy infants based on characteristic, however unusually pleomorphic polyglucosan bodies at the electron microscopic level, glycogen branching enzyme deficiency in two cases, and the identification of GBE1 mutations in two cases. Pleomorphic polyglucosan bodies in muscle fibers and macrophages, and less severe in Schwann cells and microglial cells were noted. Most of the inclusions were granular and membrane-bound; others had an irregular contour, were more electron dense and were not membrane bound, or homogenous ('hyaline'). A paracrystalline pattern of granules was repeatedly noted showing a periodicity of about 10 nm with an angle of about 60 degrees or 120 degrees at sites of changing linear orientation. Malteser crosses were noted under polarized light in the larger inclusions. Some inclusions were PAS positive and others were not. Severely atrophic muscle fibers without inclusions, but with depletion of myofibrils in the plane of section studied indicated the devastating myopathic nature of the disease. Schwann cells and peripheral axons were less severely affected as was the spinal cord. Two novel protein-truncating mutations (c.1077insT, p.V359fsX16; g.101517_127067del25550insCAGTACTAA, DelExon4-7) were identified in these families. The present findings extend previous studies indicating that truncating GBE1 mutations cause a spectrum of severe diseases ranging from generalized intrauterine hydrops to fatal perinatal hypotonia and fatal cardiomyopathy in the first months of life. SN - 1432-0533 UR - https://www.unboundmedicine.com/medline/citation/18661138/Congenital_type_IV_glycogenosis:_the_spectrum_of_pleomorphic_polyglucosan_bodies_in_muscle_nerve_and_spinal_cord_with_two_novel_mutations_in_the_GBE1_gene_ L2 - https://dx.doi.org/10.1007/s00401-008-0417-8 DB - PRIME DP - Unbound Medicine ER -