Morphologic and Clinical Aspects of Danon Disease in a Patient with a Mutation c.137G > A in the LAMP-2 Gene

Background Danon disease is caused by a primary deficiency of lysosome-associated membrane protein-2 (LAMP-2). Materials and Methods Our study describes a 19-year-old man with isolated hypertrophic cardiomyopathy, in whom we performed DNA analysis and compared results of microscopic analysis of skeletal and cardiac muscles. Results Sequencing of the LAMP-2 gene revealed a novel point mutation c.137G > A in exon 2, leading to premature stop codon. Ultrastructural analysis of cardiac and skeletal muscles revealed the presence of unusual autophagic vacuoles in both. Although some vacuoles in skeletal muscle reacted strongly with dystrophin, β-sarcoglycan, and laminin, those in cardiomyocytes showed no immunoreactivity. Conclusion Our immunohistochemical and ultrastructural findings reinforce the claim that in Danon disease the pathomechanism of chaperone-mediated autophagy in cardiomyocytes differs from that in skeletal muscle.