Glycogen storage disease with severe cardiomyopathy due to glycogenin deficiency

Glycogen storage disease with severe cardiomyopathy due to glycogenin deficiency (also known as glycogen storage disease type XV, GSD XV) is an extremely rare inherited metabolic disorder caused by mutations in the GYG1 gene, which encodes glycogenin-1, a protein essential for initiating glycogen synthesis. Glycogenin serves as a primer for glycogen chain formation, and its deficiency leads to abnormal glycogen metabolism affecting primarily the heart and skeletal muscles. The disease is characterized by severe cardiomyopathy, which can manifest as either hypertrophic or dilated cardiomyopathy, and may be accompanied by skeletal myopathy with muscle weakness. Cardiac involvement is the predominant and most life-threatening feature, with patients developing progressive heart failure. Skeletal muscle biopsies may show glycogen depletion or abnormal glycogen accumulation with polyglucosan body formation. The age of onset can vary, with some patients presenting in adulthood with cardiac symptoms or muscle weakness. There is currently no specific or curative treatment for this condition. Management is supportive and focuses on treating the cardiac manifestations, including standard heart failure therapies and, in severe cases, consideration of cardiac transplantation. Physical therapy may be beneficial for patients with skeletal muscle involvement. Due to the extreme rarity of this disease, with only a handful of cases reported in the medical literature, knowledge about the full clinical spectrum and long-term prognosis remains limited.

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