Cardiac arrhythmias in patients with Danon disease

Konrad, Torsten; Sonnenschein, Sebastian; Schmidt, Frank; Mollnau, Hanke; Bock, Karsten; Ocete, Blanca Quesada; Münzel, Thomas; Theis, C.; Rostock, Thomas

doi:10.1093/europace/euw215

Cited by 22 publications

(28 citation statements)

References 15 publications

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“…They concluded that one etiology for preexcitation pattern in these patients could have been FVP, although this was not confirmed. Interestingly, none of the female patients in their study had a WPW pattern although three out of four patients with preexcitation in our study were female …”

Section: Discussionmentioning

confidence: 93%

“…Conversely, in another series by Konrad et al, nearly all patients ( n = 7) with Danon disease had ventricular tachyarrhythmias leading to ICD placement ( n = 4). Nevertheless, none of these patients received an ICD therapy during a follow‐up period of nearly 4 years . These findings are similar to our study where placement of an ICD was performed for primary prevention based on nonsustained ventricular tachycardia, progressive septal hypertrophy and degree of fibrosis on cardiac MRI.…”

Section: Discussionmentioning

confidence: 99%

“…9 patients in their study had a WPW pattern although three out of four patients with preexcitation in our study were female. 13 Atrial arrhythmias are very frequent in Danon disease with a reported prevalence of 85% in two recent series. 13,14 Ventricular arrhythmias in patients with Danon disease is also well described.…”

Section: Discussionmentioning

confidence: 99%

“…13 Atrial arrhythmias are very frequent in Danon disease with a reported prevalence of 85% in two recent series. 13,14 Ventricular arrhythmias in patients with Danon disease is also well described.…”

Section: Discussionmentioning

confidence: 99%

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Arrhythmias and fasciculoventricular pathways in patients with Danon disease: A single center experience

Jhaveri

Herber

Zahka

et al. 2019

Cardiovasc electrophysiol

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Background Danon disease is a rare X‐linked storage disorder characterized by hypertrophic cardiomyopathy leading to arrhythmias and heart failure. A preexcitation pattern on electrocardiogram (ECG) has been described in these patients, however, invasive studies to distinguish between Wolff‐Parkinson‐White syndrome syndrome and fasciculoventricular pathways (FVP) are limited. Objectives The purpose of this study was to delineate the electrophysiological cardiac abnormalities in patients with Danon disease and to describe the presence of FVP in this population. Methods We performed a retrospective study of all patients with a confirmed diagnosis of Danon disease presenting to a single center from May 2005 to May 2018. Baseline demographics, clinical characteristics, ECG findings, and electrophysiology study (EPS) results were collected. Results Ten patients with Danon disease (30% male, average age 17.4 years) were identified. Seven patients (70%) had tachyarrhythmias including five with atrial arrhythmias and six with nonsustained ventricular tachycardia. Preexcitation pattern on ECG was found in four (40%) patients. Of these, two underwent an EPS which confirmed the presence of an FVP. One patient underwent an adenosine challenge which supported a FVP. Implantable cardioverter defibrillator was placed in five patients for primary prevention with no patients receiving an appropriate discharge. Over a follow‐up of 5.3 years, five underwent heart transplantation. Conclusions This study reports a high incidence of FVP in patients with Danon disease and preexcitation. It underscores an alternate etiology of preexcitation in this population which can potentially be diagnosed without invasive EPS testing. Future multicenter studies are needed to expand this experience.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Arrhythmias and fasciculoventricular pathways in patients with Danon disease: A single center experience

Jhaveri

Herber

Zahka

et al. 2019

Cardiovasc electrophysiol

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“…Symptoms are not prominent and are frequently overlooked or misdiagnosed as simple hypertrophic cardiomyopathy. Heart failure is an important factor affecting the prognosis of patients with Danon disease (Konrad et al, 2017). Pathological changes in the muscles of patients with Danon disease include the presence of multiple membranous autophagy vacuoles (Stokes, Taylor, McLean, D'Arcy, & Mariani, 2016).…”

mentioning

confidence: 99%

A family with Danon disease caused by a splice site mutation in LAMP2 that generates a truncated protein

Zhou

Cui

Zhao

et al. 2019

Molec Gen & Gen Med

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Background Danon disease is an X‐linked dominant hereditary condition caused by mutations in the gene encoding lysosomal‐associated membrane protein 2 ( LAMP 2), leading to failure of lysosome binding to autophagosomes, accumulation of glycogen in the heart, and abnormal cardiac function. Methods We describe identification of a mutation in LAMP 2 , c.741+1G>T, in a family with Danon disease by whole exome sequencing. Results Pathology examination of patient skeletal muscle biopsy showed myogenic damage and autophagic vacuoles with sarcolemmal features ( AVSF ). Numerous autophagic vacuoles accumulated in muscle cells were detected by electron microscopy, indicating abnormal autophagy function. Conclusion The mutation did not result in loss of mRNA exons; rather, a 6‐nucleotide (two‐codon) insertion, where the latter was a stop codon, leading to early termination of LAMP 2 protein translation. The resulting truncated protein lacks an important transmembrane domain, which will impair lysosome/autophagosome fusion, damage autophagy function, and result in the clinical manifestations of Danon disease.

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Prevalence and clinical characteristics of Danon disease among patients with left ventricular hypertrophy and concomitant electrocardiographic preexcitation

Liu

Chen

Wang

et al. 2019

Molec Gen & Gen Med

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Background Cardiac 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. Methods Electrocardiographic preexcitation was identified in 10 of 197 patients with unexplained LVH in whom genetic testing was performed using next‐generation sequencing. Results Three (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. Conclusion In 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.

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Cardiac arrhythmias in patients with Danon disease

Cited by 22 publications

References 15 publications

Arrhythmias and fasciculoventricular pathways in patients with Danon disease: A single center experience

Arrhythmias and fasciculoventricular pathways in patients with Danon disease: A single center experience

A family with Danon disease caused by a splice site mutation in LAMP2 that generates a truncated protein

Prevalence and clinical characteristics of Danon disease among patients with left ventricular hypertrophy and concomitant electrocardiographic preexcitation

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