Lafora Disease Is an Inherited Metabolic Cardiomyopathy

Abstract

Inherited metabolic storage cardiomyopathies, often clinically misdiagnosed, compose a small, but important, fraction of patients genotyped with clinical suspicion of hypertrophic cardiomyopathy (HCM, ≤1%). Overall, glycogen metabolism disorders affect energy homeostasis, primarily in skeletal muscle, heart, liver, and, less frequently, the central nervous system. These rare diseases are quite variable regarding age of onset, symptoms, morbidity, and mortality. Typical pathologic vacuoles containing glycogen or intermediary metabolites altering cardiac structure and function are usually described in Pompe, Danon, and Fabry diseases as well as in patients with mutations in PRKAG2, the regulatory γ subunit of AMP-activated protein kinase. In affected patients, these multisystem disorders may cause left ventricular hypertrophy that could accompany neuromuscular deficits, liver and/or kidney dysfunction, and abnormalities of the peripheral central nervous system