Late-onset polyglucosan body myopathy in five patients with a homozygous mutation in GYG1

Abstract

Five Sardinian patients presented in their 5th or 6th decade with progressive limb girdle muscle weakness but their muscle biopsies showed vacuolar myopathy. The more or less abundant subsarcolemmal and intermyofibrillar vacuoles showed intense, partially α-amylase resistant, PAS-positive deposits consistent with polyglucosan. The recent description of late-onset polyglucosan myopathy has prompted us to find new genetic defects in the gene (GYG1) encoding glycogenin-1, the crucial primer enzyme of glycogen synthesis in muscle. We found a single homozygous intronic mutation harbored by five patients, who, except for two siblings, appear to be unrelated but all five live in central or south Sardinian villages.

Keywords: GYG1; Glycogenin deficiency; Glycogenosis; Polyglucosan myopathy.

Copyright © 2015 Elsevier B.V. All rights reserved.

Figures

Fig. 1

Muscle MRI from Patient 5 shows fatty replacement at hip level (A), of notably the major gluteus (1) and vastus lateralis (2), and at thigh level (B), of notably the vastus lateralis (2) and the adductor magnus (3).

Fig. 2

Serial sections of vastus lateralis muscle stained strongly with PAS reaction but incompletely digested by alpha-amylase.

Fig. 3

Electron microscopy shows presence of subsarcolemmal abnormal glycogen material corresponding to polyglucosan bodies (A). At higher magnification, polyglucosan bodies are composed of poorly organized filamentous material (B).

Fig. 4

Intronic mutation (c.143 + 3G > C) indicated by arrow causes aberrant splicing of the GYG1 mRNA.