Abstract 14213: A Retrospective Natural History Study of Danon Disease

Abstract

Introduction: Danon disease (DD) is a rare X-linked dominant cardioskeletal myopathy caused by mutations in the lysosome-associated membrane protein-2 (LAMP2) gene. The purpose of this study is to characterize disease progression and outcomes in males and females with DD. Methods: Data were from the International Danon Disease Registry that includes patients from the United States and Europe consented between 2005 and 2022. Records were obtained from the first episode of care to the date of enrollment and included demographics, clinical characteristics and outcomes. Chi square and Wilcoxon testing were used for cross-sectional and mixed effects models used for longitudinal analyses. Data were censored after TXP or LVAD. Results: This study included 112 patients with a median follow up of 6.8 yrs (IQR: 2.5-12.8 yrs). Demographics and outcomes are in Table 1. Males were more likely to experience the combined heart failure outcome. At least mild ventricular dysfunction occurred in 30% of patients, and almost all patients had LV hypertrophy. Regarding arrhythmias, WPW and CIED placement were common. Over time, LVEF decreased in both sexes and LV wall thickness did not increase, although LV mass increased in males only. BNP, CPK and AST did not change. [Table 2] Conclusions: DD is a multisystem and progressive disease with potential for cardiac arrhythmias, progressive hypertrophy and ventricular dysfunction. Currently, there are no disease modifying therapies for DD, although gene therapy trials are underway. Understanding the natural history of DD is critical for informing patient selection of therapies, including heart transplantation and new gene modifying therapies.