Cardiomyopathy in glycogen storage diseases: diagnosis, prognosis, and advanced management

Glycogen storage diseases (GSDs) are a heterogeneous group of rare and often under-recognized causes of inherited cardiomyopathy characterized by pathological glycogen or autophagic vacuole accumulation of debris within various tissues, including the heart. These diseases often present as phenocopies of sarcomeric hypertrophic cardiomyopathy, though they may also manifest with dilated or mixed phenotypes. Key GSDs with cardiomyopathy include Pompe disease (GSD IIa), Danon disease (IIb), Cori/Forbes disease (GSD III), Andersen disease (GSD IV), Tarui disease (GSD VII), phosphorylase kinase deficiency (GSD IX), glycogenin-1 deficiency (GSD XV), and PRKAG2 syndrome, each presenting unique clinical trajectories. Accurate diagnosis requires integration of clinical red flags, multimodality cardiac imaging, and electrocardiography, alongside definitive diagnostic tools like enzyme screening, genetic testing, and endomyocardial biopsy. There is a dearth of evidence regarding specific treatment of each unique GSD cardiomyopathy, but emerging therapeutics across the spectrum of GSDs aim to address this need. This review covers current knowledge on the spectrum of GSD-related cardiomyopathies, discussing pathophysiology, diagnosis, and evolving treatment strategies.