Abstract
BackgroundCardiac involvement in Danon disease typically manifests as left ventricular hypertrophy (LVH) and ventricular preexcitation. This study aimed to identify patients with Danon disease among patients with LVH and concurrent electrocardiographic preexcitation.MethodsElectrocardiographic preexcitation was identified in 10 of 197 patients with unexplained LVH in whom genetic testing was performed using next‐generation sequencing.ResultsThree (3/10, 30%) patients with Danon disease were found in association with different mutations in the gene of lysosome‐associated membrane protein 2 (LAMP2). Compared to seven patients without Danon disease, these three patients presented with distinctive clinical phenotypes, including onset at an earlier age (20 ± 2 years vs. 53 ± 9 years, p < 0.001), more neurological involvements (100% vs. 0, p = 0.008), higher electrocardiographic voltages (10 ± 1 mV vs. 5 ± 1 mV, p < 0.001), wider QRS complexes (163 ± 5 ms vs. 115 ± 20 ms, p = 0.006), less common asymmetric hypertrophy (0% vs. 86%, p = 0.033), and more frequent elevation of three serum enzymes (creatine kinase, aspartate aminotransferase, and lactate dehydrogenase). Intracellular vacuoles accumulation with deficiencies of LAMP2 protein was found in both cardiac and skeletal myocytes of patients with Danon disease.ConclusionIn patients with coexistent LVH and ventricular preexcitation, Danon disease is common with distinctive clinical presentations. Comprehensive assessment of these resemble patients can provide valuable findings for early identification and clinical decision making of patients with Danon disease.
Highlights
Danon disease, caused by the mutations in the gene of lysosome‐ associated membrane protein 2 (LAMP2,Online Mendelian Inheritance in Man (OMIM)*309060), is an X‐linked dominant disorder classically characterized by the triad of cardiomyopathy, skeletal myopathy, and intellectual disability (Danon et al, 1981; Nishino et al, 2000; Tanaka et al, 2000)
Genetic testing of 10 patients with unexplained left ventricular hypertrophy (LVH) and preexcited ECG patterns led to the identification of three (30%) individuals with Danon disease caused by different lysosome‐associated membrane protein 2 (LAMP2) mutations, including a previously unreported mutation
Deficiencies of LAMP2 protein with resultant intracellular vacuoles accumulation in both cardiac and skeletal myocytes were found to account for the development of the disease in our patients
Summary
Dr Liu receives research grants from the National Natural Science Foundation of China (NSFC‐81400259) and Guangdong Province (2014A030310470). Dr Wu receives research grants from the Science and Technology Programs of Guangdong Province (No 2014B070705005) and Guangzhou City (No 201508020261).
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