Glycogenin-1 deficiency mimicking limb-girdle muscular dystrophy

Claire Lefeuvre (1) , Stéphane Schaeffer (2) , Robert Yves Carlier (3, 1) , Maxime Fournier (2) , Françoise Chapon (4) , Valérie V. Biancalana (5, 6, 7) , Guillaume Nicolas (3, 1, 8) , Eduardo Malfatti (3, 8, 1) , Pascal Laforêt (3, 1, 8)

1 Hôpital Raymond Poincaré [AP-HP]
2 Service de Neurologie [CHU Caen]
3 END-ICAP - Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées
4 Laboratoire d'Anatomie Pathologique [CHU Caen]
5 Laboratoire de Diagnostic Génétique [CHU Strasbourg]
6 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
7 FMTS - Fédération de Médecine Translationnelle de Strasbourg
8 UVSQ - Université de Versailles Saint-Quentin-en-Yvelines

Glycogen storage disease type XV (GSD XV) is a recently described muscle glycogenosis due to glycogenin-1 (GYG1) deficiency characterized by the presence of polyglucosan bodies on muscle biopsy (Polyglucosan body myopathy-2, PGBM2). Here we describe a 44 year-old man with limb-girdle muscle weakness mimicking a limb-girdle muscular dystrophy (LGMD), and early onset exertional myalgia. Neurologic examination revealed a waddling gait with hyperlordosis, bilateral asymmetric scapular winging, mild asymmetric deltoid and biceps brachii weakness, and pelvic-girdle weakness involving the gluteal muscles and, to a lesser extent, the quadriceps. Serum creatine kinase levels were slightly elevated. Electrophysiological examination showed a myopathic pattern. There was no cardiac or respiratory involvement. Whole-body muscle MRI revealed atrophy and fat replacement of the tongue, biceps brachii, pelvic girdle and erector spinae. A deltoid muscle biopsy showed the presence of PAS-positive inclusions that remained non-digested with alpha-amylase treatment. Electron microscopy studies confirmed the presence of polyglucosan bodies. A diagnostic gene panel designed by the Genetic Diagnosis Laboratory of Strasbourg University Hospital (France) for 210 muscular disorders genes disclosed two heterozygous, pathogenic GYG1 gene mutations (c.304G>C;p.(Asp102His) + c.164_165del). Considering the clinical heterogeneity found in the previously described 38 GYG-1 deficient patients, we suggest that GYG1 should be systematically included in targeted NGS gene panels for LGMDs, distal myopathies, and metabolic myopathies.

Mots clés: Polyglucosan body myopathy-2; PBM-2; Glycogen storage disease type XV; Glycogenin-1; GSD XV; GYG-1; Neuromuscular disease

Domaines: Sciences du Vivant [q-bio]

Claire Lefeuvre, Stéphane Schaeffer, Robert Yves Carlier, Maxime Fournier, Françoise Chapon, et al.. Glycogenin-1 deficiency mimicking limb-girdle muscular dystrophy. Molecular Genetics and Metabolism Reports, 2020, 24, ⟨10.1016/j.ymgmr.2020.100597⟩. ⟨hal-02677121⟩