Glycogen synthesis in glycogenin 1 deficient patients; a role for glycogenin 2 in muscle.

Related Articles

Glycogen synthesis in glycogenin 1 deficient patients; a role for glycogenin 2 in muscle.

J Clin Endocrinol Metab. 2017 Apr 27;:

Authors: Krag TO, Ruiz CR, Vissing J

Abstract
Context: Glycogen storage disease type XV (GSD XV) is a rare disease caused by mutations in the GYG1 gene that codes for the core molecule of muscle glycogen, glycogenin 1. Nonetheless, glycogen is present in muscles of glycogenin 1 deficient patients, suggesting an alternative for glycogen build-up. A likely candidate is glycogenin 2, an isoform expressed in liver and heart, but not in healthy skeletal muscle.
Objective: We wanted to investigate the formation of glycogen and changes in glycogen metabolism in patients with GSD XV.
Design, setting, and Patients: Two patients with mutations in the GYG1 gene were investigated for histopathology, ultrastructure and expression of proteins involved in glycogen synthesis and metabolism.
Results: Apart from occurrence of polyglucosan bodies in few fibers, glycogen appeared normal in most cells and the concentration was normal in patients with GSD XV. We found that glycogenin 1 was absent, but glycogenin 2 present in the patients, while the opposite was the case in healthy controls. Electron microscopy revealed that glycogen was present between and not inside myofibrils in type II fibers compromising the ultrastructure of these fibers, and only type I fibers contained polyglucosan bodies. We also found significant changes to the expression levels of several enzymes directly involved in glycogen and glucose metabolism.
Conclusions: This is the first report demonstrating expression of glycogenin 2 in glycogenin 1 deficient patients, suggesting that glycogenin 2 rescues the formation of glycogen in patients with glycogenin 1 deficiency.

PMID: 28453664 [PubMed - as supplied by publisher]

http://ift.tt/2pKXROc