Serial Cardiovascular Magnetic Resonance Evolution of Late-Onset Female Danon Disease Initially Diagnosed as Hypertrophic Cardiomyopathy: A Case Report

Background/Objectives: Danon disease is a rare X-linked lysosomal disorder caused by pathogenic variants in LAMP2. In women, cardiac involvement may occur later in life and may resemble sarcomeric hypertrophic cardiomyopathy (HCM), particularly when extracardiac manifestations are absent or subtle. A 42-year-old woman presented with chest discomfort in 2017 and was initially diagnosed with hypertrophic cardiomyopathy (HCM). She underwent serial 3.0-T cardiovascular magnetic resonance (CMR) over an 8-year period. Initial CMR showed left-ventricular hypertrophy, preserved left-ventricular ejection fraction (65.0%), increased native T1 and T2 relaxation times, extracellular volume (ECV) of 24.9%, and patchy apical late gadolinium enhancement (LGE extent, 12.35%). Five years later, worsening dyspnea was accompanied by increased left-ventricular mass index, higher native T1 and ECV, greater LGE extent (15.18%), and slow atrial fibrillation with ventricular ectopy on Holter monitoring. Genetic testing identified a likely pathogenic LAMP2 variant, c.928G>A (p.Val310Ile), supporting the diagnosis of Danon disease in the clinical context. During a subsequent readmission three years later with acute amaurosis and dyspnea, no definite neurologic cause was identified in the available record. Repeat CMR showed the highest recorded native T1 and ECV values and diffuse LGE with relatively less interventricular-septal involvement, particularly in the basal septum (LGE extent, 24.59%); repeat Holter monitoring showed frequent long R-R intervals and ventricular escape beats. Because of progressive imaging and electrical deterioration, implantable cardioverter-defibrillator therapy and heart-transplantation assessment were recommended, and the patient ultimately chose to proceed with pre-transplant assessment in December 2025. Conclusions: Female LAMP2-related Danon disease may initially resemble HCM, but differs from it with diffusely abnormal T1/ECV measurements. Follow up in our case revealed progressive storage cardiomyopathy with diffuse myocardial injury and clinically relevant bradyarrhythmia.