Narrative review of glycogen storage disorder type III with a focus on neuromuscular, cardiac and therapeutic aspects

J Inherit Metab Dis. 2021 May;44(3):521-533. doi: 10.1002/jimd.12355. Epub 2021 Jan 3.

Abstract

Glycogen storage disorder type III (GSDIII) is a rare inborn error of metabolism due to loss of glycogen debranching enzyme activity, causing inability to fully mobilize glycogen stores and its consequent accumulation in various tissues, notably liver, cardiac and skeletal muscle. In the pediatric population, it classically presents as hepatomegaly with or without ketotic hypoglycemia and failure to thrive. In the adult population, it should also be considered in the differential diagnosis of left ventricular hypertrophy or hypertrophic cardiomyopathy, myopathy, exercise intolerance, as well as liver cirrhosis or fibrosis with subsequent liver failure. In this review article, we first present an overview of the biochemical and clinical aspects of GSDIII. We then focus on the recent findings regarding cardiac and neuromuscular impairment associated with the disease. We review new insights into the pathophysiology and clinical picture of this disorder, including symptomatology, imaging and electrophysiology. Finally, we discuss current and upcoming treatment strategies such as gene therapy aimed at the replacement of the malfunctioning enzyme to provide a stable and long-term therapeutic option for this debilitating disease.

Keywords: cardiomyopathy; gene therapy; glycogen storage disorder; hypoglycemia; metabolic disease; myopathy.

Publication types

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

MeSH terms

  • Adult
  • Animals
  • Child
  • Disease Models, Animal
  • Genetic Therapy / methods*
  • Glycogen Storage Disease Type III / metabolism
  • Glycogen Storage Disease Type III / physiopathology
  • Glycogen Storage Disease Type III / therapy*
  • Hepatomegaly / metabolism
  • Humans
  • Hypoglycemia / metabolism
  • Liver / metabolism
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiopathology*
  • Muscular Diseases / metabolism