Malignant cardiac phenotypic expression of Danon disease (LAMP2 cardiomyopathy)

Abstract

IntroductionDanon disease is an X-linked lysosomal condition that causes a deficiency of lysosome-associated membrane protein 2 (LAMP2) gene. It is characterized clinically by a triad of skeletal myopathy, cardiomyopathy, and intellectual disability. MethodsWe examined clinical, echocardiographic, and genetic data on 5 patients with Danon disease, highlighting their clinical course and outcomes. ResultsAll patients presented phenotypically with hypertrophic cardiomyopathy and later developed systolic dysfunction. The mean age at diagnosis was 19years (11–31years). All patients had diastolic dysfunction (mean e’ of 5cm/s [3.5–6cm/s], mean E/e′ of 17 [15–21]). Three patients required cardiac transplantation (ages 15, 27, and 42). Of the two deaths in this group, both were in women. ConclusionWe highlight the aggressive cardiac phenotype of Danon disease in our clinical experience with rapid progression to end-stage cardiomyopathy; this progression occurred in both men and women. A timely diagnosis and an early referral for cardiac transplantation is crucial for improved outcomes.