Glycogen storage disease with hypertrophic cardiomyopathy

Glycogen storage disease with hypertrophic cardiomyopathy (Orphanet code 217572) is a grouping of rare inherited metabolic disorders characterized by abnormal glycogen accumulation that predominantly affects the heart, leading to hypertrophic cardiomyopathy (thickening of the heart muscle). Several distinct genetic conditions fall under this umbrella, including Danon disease (caused by LAMP2 gene mutations), PRKAG2 cardiac glycogen storage disease, and other forms of glycogen storage disease that feature prominent cardiac involvement. The abnormal storage of glycogen within cardiac muscle cells disrupts normal heart structure and function, leading to progressive thickening of the ventricular walls, impaired cardiac output, and potentially life-threatening arrhythmias. Key symptoms include progressive heart failure, exercise intolerance, shortness of breath, palpitations, chest pain, and in some cases skeletal muscle weakness and intellectual disability depending on the specific underlying genetic cause. Cardiac conduction abnormalities, including Wolff-Parkinson-White syndrome, are frequently observed in certain subtypes such as PRKAG2-related disease and Danon disease. Some forms may also involve the liver and skeletal muscles, reflecting the systemic nature of glycogen metabolism. Treatment is largely supportive and symptom-directed. Management may include medications for heart failure and arrhythmias, implantable cardioverter-defibrillators (ICDs) to prevent sudden cardiac death, and in severe cases, heart transplantation. Enzyme replacement therapy is available for some related glycogen storage disorders such as Pompe disease. Genetic counseling is recommended for affected families. Prognosis varies significantly depending on the specific genetic subtype, with some forms progressing rapidly in childhood while others have a more indolent course into adulthood.

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