A new phenotype of muscle glycogen synthase deficiency (GSD0B) characterized by an adult onset myopathy without cardiomyopathy

Neuromuscul Disord. 2022 Jul;32(7):582-589. doi: 10.1016/j.nmd.2022.03.008. Epub 2022 Mar 31.

Abstract

Muscle Glycogenosis type 0 (GSD0B) is an extremely rare disorder first recognized in 2007 in three siblings with childhood onset and severe cardiomyopathy. Since then, a few cases with severe cardiac involvement and premature death have been reported. We describe two unrelated cases presenting with an adult-onset myopathy with no heart involvement. Clinical features were quite similar in both patients, mainly characterized by early fatigability, myalgia and muscle weakness. Muscle biopsy revealed marked glycogen depletion in nearly all myofibers. Biochemical assay demonstrated a marked reduction of Glycogen Synthase (GS) activity. Sequence analysis of GYS1 revealed two new variants: a homozygous G to C substitution in the splice donor consensus site (c.678+1G>C) in patient1 and a homozygous missense variant c.630G>C in exon 3 (p. Asp145His) in patient 2. This study describes a new phenotype of muscle GSD0B presenting with adult onset, proximal myopathy, no cardiac abnormalities and a quite benign disease course. This report highlights the importance of a systematic diagnostic approach that includes muscle morphology and enzymatic assay to facilitate the identification of adult patients with GSD0B.

Keywords: GSD0B; Metabolic myopathy; Muscle glycogenosis; Muscle morphologic studies; Muscle weakness.

Publication types

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

MeSH terms

  • Cardiomyopathies* / diagnosis
  • Cardiomyopathies* / genetics
  • Cardiomyopathies* / pathology
  • Child
  • Glycogen Storage Disease* / diagnosis
  • Glycogen Storage Disease* / genetics
  • Glycogen Storage Disease* / pathology
  • Glycogen Synthase / deficiency
  • Glycogen Synthase / genetics
  • Humans
  • Muscle, Skeletal / pathology
  • Muscular Diseases* / diagnosis
  • Muscular Diseases* / genetics
  • Muscular Diseases* / pathology
  • Phenotype

Substances

  • Glycogen Synthase

Supplementary concepts

  • Glycogen Storage Disease 0, Muscle