Two young women with severe Danon disease initially suspected to have cardiac amyloidosis: a case report and literature review

Background Danon disease is a rare X-linked dominant lysosomal storage disorder caused by LAMP2 mutations and characterized by cardiomyopathy, skeletal myopathy, and intellectual disability. This study reports two Chinese cases of Danon disease that were initially suspected as cardiac amyloidosis. Methods Clinical data were collected, LAMP2 genetic analysis was performed and literatures were reviewed. Results Both patients presented with mainly cardiac symptoms in adulthood. Laboratory tests showed elevated levels of creatine kinase isoenzyme, troponin T, lactate dehydrogenase, hydroxybutyrate dehydrogenase, aspartate aminotransferase, and N-terminal pro-B-type natriuretic peptide. Cardiac MRI revealed diffuse left ventricular wall thickening and myocardial late gadolinium enhancement. Histopathology showed hypertrophied cardiomyocytes with disarray, vacuolar degeneration, enlarged, hyperchromatic nuclei, and fibrosis. Electron microscopy demonstrated autophagic vacuoles with sarcolemmal features-like structures, myelin-like figures resembling zebra bodies and accumulation of glycogen granules. Immunohistochemistry showed partial loss of LAMP2 expression. Genetic testing identified two rare heterozygous LAMP2 variants: c.3G > T in exon 1 (variant of uncertain significance) and c.446del in exon 4 (likely pathogenic). Both patients underwent heart transplantation and remained alive at follow-up. Conclusions These rare LAMP2 variants expand the mutational spectrum of Danon disease and highlight the need for genetic counseling. Endomyocardial biopsy is valuable for diagnosis, while genetic testing is required for definitive confirmation.