Myopathy with Polyglucosan Bodies

Clinical History

This 65-year-old patient with a history of severe osteoarthritis presented with muscle aches. Muscle biopsy was performed during hip replacement surgery to evaluate for possible myopathy.

What are the structures seen in the provided H&E, PASd, Toluidine blue stained thick section and EM images?

Answer:

The PAS positive material identified in this patient’s muscle biopsy is consistent with the presence of “polyglucosan bodies.”

Accumulation of polyglucosan bodies may occur in multiple tissue types, including skeletal muscle, cardiac muscle, peripheral nerve and brain, and may be caused be pathogenic variants (disease causing mutations) in multiple genes, including GYG1, GBE1, RBCK1, PFKM, EPM2A, EPM2B, PRDM8 and PRKAG2).

Reference(s) / additional reading:

• Akman HO, Aykit Y, Amuk OC, Malfatti E, Romero NB, Maioli MA, Piras R, DiMauro S, Marrosu G. Late-onset polyglucosan body myopathy in five patients with a homozygous mutation in GYG1. Neuromuscul Disord. 2016 Jan;26(1):16-20. doi: 10.1016/j.nmd.2015.10.012. Epub 2015 Nov 10. PMID: 26652229; PMCID: PMC4724519.Hedberg-Oldfors C, Oldfors A.
• Polyglucosan storage myopathies. Mol Aspects Med. 2015 Dec;46:85-100. doi: 10.1016/j.mam.2015.08.006. Epub 2015 Aug 13. PMID: 26278982.
• Nicolau S, Tracy JA, Pisapia DJ, Tanji K, Milone M. GYG1: A distal myopathy with polyglucosan bodies. JIMD Rep. 2020 May 13;55(1):88-90. doi: 10.1002/jmd2.12129. PMID: 32905144; PMCID: PMC7463053.
• Cenacchi G, Papa V, Costa R, Pegoraro V, Marozzo R, Fanin M, Angelini C. Update on polyglucosan storage diseases. Virchows Arch. 2019 Dec;475(6):671-686. doi: 10.1007/s00428-019-02633-6. Epub 2019 Jul 30. PMID: 31363843.
• Souza PVS, Badia BML, Farias IB, Pinto WBVR, Oliveira ASB, Akman HO, DiMauro S. GBE1-related disorders: Adult polyglucosan body disease and its neuromuscular phenotypes. J Inherit Metab Dis. 2021 May;44(3):534-543. doi: 10.1002/jimd.12325. Epub 2020 Nov 13. PMID: 33141444.
• Laforêt P, Malfatti E, Vissing J. Update on new muscle glycogenosis. Curr Opin Neurol. 2017 Oct;30(5):449-456. doi: 10.1097/WCO.0000000000000484. PMID: 28737584.