TY - JOUR
T1 - Glycogen synthesis in glycogenin 1-deficient patients
T2 - A role for glycogenin 2 in muscle
AU - Krag, Thomas O.
AU - Ruiz-Ruiz, Cristina
AU - Vissing, John
PY - 2017
Y1 - 2017
N2 - Context: Glycogen storage disease (GSD) type 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 buildup. A likely candidate is glycogenin 2, an isoform expressed in the 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 type 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 (PG) bodies in few fibers, glycogen appeared normal in most cells, and the concentration was normal in patients with GSD type XV. We found that glycogenin 1 was absent, but glycogenin 2 was present in the patients, whereas 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 PG bodies. We also found significant changes to the expression levels of several enzymes directly involved in glycogen and glucose metabolism. Conclusions: To our knowledge, 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.
AB - Context: Glycogen storage disease (GSD) type 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 buildup. A likely candidate is glycogenin 2, an isoform expressed in the 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 type 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 (PG) bodies in few fibers, glycogen appeared normal in most cells, and the concentration was normal in patients with GSD type XV. We found that glycogenin 1 was absent, but glycogenin 2 was present in the patients, whereas 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 PG bodies. We also found significant changes to the expression levels of several enzymes directly involved in glycogen and glucose metabolism. Conclusions: To our knowledge, 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.
U2 - 10.1210/jc.2017-00399
DO - 10.1210/jc.2017-00399
M3 - Journal article
C2 - 28453664
AN - SCOPUS:85026904129
SN - 0021-972X
VL - 102
SP - 2690
EP - 2700
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 8
ER -