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.


Adult polyglucosan body disease (APBD) represents a complex autosomal recessive inherited neurometabolic disorder due to homozygous or compound heterozygous pathogenic variants in GBE1 gene, resulting in deficiency of glycogen-branching enzyme and secondary storage of glycogen in the form of polyglucosan bodies, involving the skeletal muscle, diaphragm, peripheral nerve (including autonomic fibers), brain white matter, spinal cord, nerve roots, cerebellum, brainstem and to a lesser extent heart, lung, kidney, and liver cells. The diversity of new clinical presentations regarding neuromuscular involvement is astonishing and transformed APBD in a key differential diagnosis of completely different clinical conditions, including axonal and demyelinating sensorimotor polyneuropathy, progressive spastic paraparesis, motor neuronopathy presentations, autonomic disturbances, leukodystrophies or even pure myopathic involvement with limb-girdle pattern of weakness. This review article aims to summarize the main clinical, biochemical, genetic, and diagnostic aspects regarding APBD with special focus on neuromuscular presentations.

Keywords: GBE1 gene; glycogen; glycogen storage disease; motor neuron disease; neurogenetics; polyglucosan body disease.

Publication types

  • Review

MeSH terms

  • Adult
  • Brain / pathology
  • Glycogen Debranching Enzyme System / genetics*
  • Glycogen Storage Disease / genetics*
  • Glycogen Storage Disease / pathology
  • Glycogen Storage Disease / physiopathology*
  • Humans
  • Muscle, Skeletal / pathology
  • Nervous System Diseases / genetics*
  • Nervous System Diseases / pathology
  • Nervous System Diseases / physiopathology*
  • Peripheral Nerves / pathology
  • Phenotype
  • Spinal Cord / pathology


  • Glycogen Debranching Enzyme System
  • GBE1 protein, human

Supplementary concepts

  • Polyglucosan Body Disease, Adult Form