Glycogenin-1 deficiency: a case report and review of the literature.

Pathogenic biallelic variants in GYG1, encoding for glycogenin-1, are associated with polyglucosan bodies myopathy characterized by muscle accumulation of deposits of amylopectin-like polysaccharides (MIM 616199). So far, only few cases (<50) with molecular defects in GYG1 have been reported. The proband is a 79-year-old Italian woman presenting with subacute onset of diffuse soreness, weakness in the upper limbs and diffuse muscle atrophy without cardiac or respiratory involvement. Electromyography showed myopathic features. Muscle biopsy revealed several type I muscle fibers containing intensely PAS-positive, diastase-resistant vacuoles of variable dimension. Ultrastructural analysis showed vacuoles with granular-fibrillar storage material localized in subsarcolemmal and intermyofibrillar areas, small amounts of free glycogen and jagged Z-line appearance of some sarcomeres. Clinical exome sequencing revealed two heterozygous pathogenic variants in GYG1. Our findings provide clinical and molecular characterization of a novel case of GYG1-related polyglucosan bodies myopathy and highlight the histological clues leading to the diagnosis of this rare clinical phenotype.