Dysregulation of glycogen metabolism in cardiomyopathy caused by glycogenin-1 (GYG1) missense variants.
Kittichate Visuttijai, Carola Hedberg-Oldfors, Oscar Braun et al.
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Case in brief
The report describes a new case of glycogen storage disease type 15 (GSD15), alongside analysis of heart explants from two previously reported patients. GSD15 results from pathogenic GYG1 variants and is associated with cardiomyopathy and abnormal glycogen and polyglucosan storage in cardiomyocytes. Mass spectrometry and immunohistochemistry showed that the storage material was enriched in proteins involved in glycogen metabolism, as well as p62 and desmin. Whole-myocardial analyses found increased cardiomyopathy-associated biomarkers and reduced mitochondrial proteins. The authors link these findings to dysregulated glycogen turnover, impaired energy metabolism, structural disruption, progressive fibrosis, and congestive heart failure.
What made this case unusual
The storage material itself was enriched in multiple glycogen-metabolism proteins, including glycogenin-1, glycogen synthase, and glycogen phosphorylase, alongside p62 and desmin; the study found no evidence of increased autophagocytosis.
Diagnostic / clinical pearl
In GYG1-related GSD15, cardiomyocyte glycogen and polyglucosan deposits contain enriched glycogen-metabolism proteins, supporting dysregulated glycogen turnover as part of the disease pathology.