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Eric Adler - One of the best experts on this subject based on the ideXlab platform.
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Danon Disease-Associated LAMP-2 Deficiency Drives Metabolic Signature Indicative of Mitochondrial Aging and Fibrosis in Cardiac Tissue and hiPSC-Derived Cardiomyocytes
Journal of clinical medicine, 2020Co-Authors: Giorgia Del Favero, Luisa Mestroni, Teisha J. Rowland, Eric Adler, Alois Bonifacio, Shanshan Gao, Kunhua Song, Valter Sergo, Orfeo Sbaizero, Matthew R.g. TaylorAbstract:Danon Disease is a severe X-linked disorder caused by deficiency of the lysosome-associated membrane protein-2 (LAMP-2). Clinical manifestations are phenotypically diverse and consist of hypertrophic and dilated cardiomyopathies, skeletal myopathy, retinopathy, and intellectual dysfunction. Here, we investigated the metabolic landscape of Danon Disease by applying a multi-omics approach and combined structural and functional readouts provided by Raman and atomic force microscopy. Using these tools, Danon patient-derived cardiac tissue, primary fibroblasts, and human induced pluripotent stem cells differentiated into cardiomyocytes (hiPSC-CMs) were analyzed. Metabolic profiling indicated LAMP-2 deficiency promoted a switch toward glycolysis accompanied by rerouting of tryptophan metabolism. Cardiomyocytes’ energetic balance and NAD+/NADH ratio appeared to be maintained despite mitochondrial aging. In turn, metabolic adaption was accompanied by a senescence-associated signature. Similarly, Danon fibroblasts appeared more stress prone and less biomechanically compliant. Overall, shaping of both morphology and metabolism contributed to the loss of cardiac biomechanical competence that characterizes the clinical progression of Danon Disease.
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Prevalence and Outcomes of Patients with Wolff-Parkinson-White in Danon Disease: Results of a Retrospective Analysis.
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2020Co-Authors: Mary Brooks, Douglas Darden, Victor Escobedo, Chrystelle Bougalt, K Hong, Eric AdlerAbstract:Danon Disease is a rare X-linked myopathy caused by defects in the lysosome-associated membrane 2 (LAMP2) gene. It is strongly associated with hypertrophic cardiomyopathy as well as Wolff-Parkinson-White (WPW) syndrome, but the prevalence of WPW in Danon is unclear. This study examined the prevalence of WPW and associated outcomes in a cohort of patients with Danon Disease. Records were reviewed for 41 patients with confirmed Danon Disease enrolled in a previously described retrospective registry, 31 of which had at least one electrocardiogram (EKG) on file. EKGs were assessed for the presence of WPW, as well as left and right ventricular hypertrophy (LVH, RVH), or both. WPW was defined as a PR interval ≤ 120 milliseconds, QRS interval ≥120 milliseconds, and delta wave. Charts were reviewed for internal cardiac defibrillator (ICD) placement, heart transplantation, and death. These outcomes were evaluated between patients with and without WPW on EKG using chi-square analysis, with p <0.05 noted to be significant. EKG criteria for LVH, RVH or both was met in 10 of the 11 WPW patients, compared to 9 of the 20 without WPW (p=0.012). ICD devices were present in 9 of the 11 WPW patients, 3 of which were placed for secondary prevention, compared to 9 of the 20 patients without WPW (p=0.119). Six of the 11 WPW patients eventually underwent heart transplant, compared to 4 of the 20 without WPW (p=0.058). Only one death was noted in this cohort, and was determined to not be cardiac related. In a cohort of patients with Danon Disease, approximately one-third had WPW syndrome on EKG. Those with WPW on EKG had higher rates of EKG criteria for LVH, RVH or both and were more likely to require advanced therapies such as ICD placement and cardiac transplant. Larger studies involving WPW in Danon Disease should seek to better characterize these outcomes. Copyright © 2020. Published by Elsevier Inc.
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description of left ventricular strain in Danon Disease insights from a global registry
Journal of the American College of Cardiology, 2020Co-Authors: Quan M. Bui, Kimberly N. Hong, Victor Escobedo, Michela Brambatti, M. Taylor, Megan Kraushaar, Andrew M. Kahn, Chrystelle Bougault, Liz Covarrubias, Eric AdlerAbstract:Danon Disease (DD) is a rare X-linked disorder due to mutations in the Lysosomal Associated Membrane Protein 2 (LAMP-2) gene and causes severe cardiac manifestations. Longitudinal strain (LS) has emerged as a diagnostic and prognostic tool in various cardiomyopathies. A retrospective, international
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WOLFF-PARKINSON-WHITE IN INDIVIDUALS WITH Danon Disease IS A MARKER OF Disease SEVERITY
Journal of the American College of Cardiology, 2020Co-Authors: Mary Brooks, Douglas Darden, Kimberly N. Hong, Victor Escobedo, Michela Brambatti, Chrystelle Bougalt, Eric AdlerAbstract:Danon Disease is a rare X-linked myopathy associated with hypertrophic cardiomyopathy and Wolff-Parkinson-White (WPW) syndrome. The prevalence of WPW in Danon Disease is unclear. This study examined the prevalence of WPW and associated outcomes in a cohort of Danon Disease patients. EKGs of 28
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Prevalence and Outcomes of Patients with Wolff-Parkinson-White in Danon Disease: Results of a Retrospective Analysis.
The Journal of Heart and Lung Transplantation, 2020Co-Authors: Mary Brooks, Douglas Darden, Kimberly N. Hong, Victor Escobedo, Chrystelle Bougalt, Eric AdlerAbstract:Purpose Danon Disease is a rare X-linked myopathy caused by defects in the lysosome-associated membrane 2 (LAMP2) gene. It is strongly associated with hypertrophic cardiomyopathy as well as Wolff-Parkinson-White (WPW) syndrome, but the prevalence of WPW in Danon is unclear. This study examined the prevalence of WPW and associated outcomes in a cohort of patients with Danon Disease. Methods Records were reviewed for 41 patients with confirmed Danon Disease enrolled in a previously described retrospective registry, 31 of which had at least one electrocardiogram (EKG) on file. EKGs were assessed for the presence of WPW, as well as left and right ventricular hypertrophy (LVH, RVH), or both. WPW was defined as a PR interval ≤ 120 milliseconds, QRS interval ≥120 milliseconds, and delta wave. Charts were reviewed for internal cardiac defibrillator (ICD) placement, heart transplantation, and death. These outcomes were evaluated between patients with and without WPW on EKG using chi-square analysis, with p Results EKG criteria for LVH, RVH or both was met in 10 of the 11 WPW patients, compared to 9 of the 20 without WPW (p=0.012). ICD devices were present in 9 of the 11 WPW patients, 3 of which were placed for secondary prevention, compared to 9 of the 20 patients without WPW (p=0.119). Six of the 11 WPW patients eventually underwent heart transplant, compared to 4 of the 20 without WPW (p=0.058). Only one death was noted in this cohort, and was determined to not be cardiac related. Conclusion In a cohort of patients with Danon Disease, approximately one-third had WPW syndrome on EKG. Those with WPW on EKG had higher rates of EKG criteria for LVH, RVH or both and were more likely to require advanced therapies such as ICD placement and cardiac transplant. Larger studies involving WPW in Danon Disease should seek to better characterize these outcomes.
Ichizo Nishino - One of the best experts on this subject based on the ideXlab platform.
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Lysosomal membrane disorders: lysosome-associated membrane protein-2 deficiency (Danon Disease)
Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease, 2020Co-Authors: Kazuma Sugie, Ichizo NishinoAbstract:Abstract Danon Disease has been referred to as “glycogen storage Disease IIb” (GSDIIb), but it is not actually a glycogen storage Disease, as it is caused by the primary deficiency of a lysosomal membrane protein, lysosome-associated membrane protein-2. Danon Disease is inherited as X-linked dominant; thus males are more severely affected than females, although females develop symptoms at a later onset. Patients with Danon Disease typically show a triad of findings: hypertrophic cardiomyopathy, muscle weakness, and mental retardation. Other organs such as the liver and retina can also be involved. Heart transplantation is the only reliable treatment after the occurrence of heart failure and should be considered as early as possible due to its rapid progression. Pathologically, Danon Disease is characterized by autophagic vacuoles with unique sarcolemmal features (AVSFs). AVSFs express virtually all sarcolemmal proteins, in addition to acetylcholinesterase, on their vacuolar membranes. AVSFs delineate a group of autophagic vacuolar myopathies, including Danon Disease.
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Danon Disease: a phenotypic expression of LAMP-2 deficiency
Acta Neuropathologica, 2015Co-Authors: Yukari Endo, Akiko Furuta, Ichizo NishinoAbstract:Danon Disease is an X-linked disorder clinically characterized by the triad of hypertrophic cardiomyopathy, myopathy, and intellectual disability. Cardiomyopathy is a severe and life-threatening problem, for which cardiac transplantation is the only therapeutic option. The most striking finding in muscle biopsy samples is small basophilic granules scattered in myofibers, which are in fact small autophagic vacuoles surrounded by membranes with sarcolemmal features characterized by the recruitment of sarcolemmal proteins and acetylcholine esterase and by the presence of basal lamina on its luminal side. The mechanism underlying the formation of these autophagic vacuoles with unique sarcolemmal features (AVSF) still remains a mystery and its origin is unknown. In heart, cardiomyocytes show dramatically increased vacuolation and degenerative features, including myofibrillar disruption and lipofuscin accumulation. In brain, pale granular neurons and neurons with lipofuscin-like granules may be seen. Danon Disease is caused by loss-of-function mutations in the LAMP2 gene, which encodes lysosome-associated membrane protein 2 (LAMP-2), a single-spanned transmembrane protein localized in the limiting membranes of lysosomes and late endosomes. Most mutations lead to splicing defects or protein truncation, resulting in a loss of transmembrane and/or cytoplasmic domains, leading to LAMP-2 protein deficiency. LAMP-2 is required for the maturation of autophagosomes by fusion with lysosomes; therefore, LAMP-2 deficiency leads to a failure in macroautophagy. There are three LAMP-2 isoforms, LAMP-2A, -2B, and -2C. Clinical features of Danon Disease are thought to be mediated by loss of the LAMP-2B isoform which is the major isoform expressed in muscle. It is also known that LAMP-2 plays a role in chaperone-mediated autophagy and RNA- and DNA-targeting autophagy. However, the precise pathophysiological mechanism through which LAMP-2 deficiency causes Danon Disease is still not fully understood and its elucidation would promote the development of new therapies.
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A 13-YEAR-OLD GIRL WITH PROXIMAL WEAKNESS AND HYPERTROPHIC CARDIOMYOPATHY WITH Danon Disease
Muscle & nerve, 2010Co-Authors: Hunmin Kim, Ichizo Nishino, Anna Cho, Byung Chan Lim, Min Jung Kim, Ki Joong Kim, Yong Seung Hwang, Jong-hee ChaeAbstract:Danon Disease is caused by deficiency of lyso- some-associated membrane protein-2 (LAMP-2). It is character- ized clinically by cardiomyopathy, myopathy, and mental retardation in boys. Herein we report a 13-year-old female patient with Danon Disease who presented with early-onset skeletal myopathy and cardiomyopathy. She had a de novo novel mutation in the LAMP2 gene, and her muscles showed many autophagic vacuoles with sarcolemmal features and com- plete absence of LAMP-2 expression. To the best of our knowl- edge, this girl is one of the earliest-onset manifesting carriers of Danon Disease with typical muscle pathology. Muscle Nerve 41: 879-882, 2010
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Novel Lamp-2 gene mutation and successful treatment with heart transplantation in a large family with Danon Disease.
Muscle & nerve, 2006Co-Authors: Andoni Echaniz-laguna, Ichizo Nishino, Philippe Charron, Michel Mohr, Eric Epailly, Pascale Richard, Christophe Guiraud-chaumeil, Christine TranchantAbstract:Lysosome-associated membrane protein-2 deficiency (LAMP-2 deficiency), or Danon Disease, is a rare X-linked lysosomal Disease characterized by cardiomyopathy, vacuolar myopathy, and mental retardation. Less than 20 families with mutations of the Lamp-2 gene have been reported. We describe a family from Sardinia with eight affected patients (4 females and 4 males) and a novel mutation in exon 2 of the Lamp-2 gene (c.102_103delAG). Females developed isolated cardiomyopathy in adulthood, whereas males presented with cardiomyopathy, myopathy, and mental retardation before the age of 20 years. Cardiomyopathy was lethal in three females in their 40s and in three males before the age 20 years. One patient was successfully treated by heart transplantation with more than 5-year follow-up. This study demonstrates that Danon Disease is a frequently fatal condition that is potentially treatable with heart transplantation. Muscle Nerve, 2006
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Characterization of Danon Disease in a male patient and his affected mother
Neuromuscular disorders : NMD, 2003Co-Authors: Kazuma Sugie, Ayaka Yamamoto, Megumu Ogawa, Michio Hirano, Tateo Koori, Kiyoharu Inoue, Ikuya Nonaka, Ichizo NishinoAbstract:Danon Disease, primary lysosome-associated membrane protein-2 (LAMP-2) deficiency, is histologically characterized by unusual vacuoles bound by membranes with sarcolemmal features in skeletal muscle. We studied skeletal muscle specimens from a male patient with genetically confirmed Danon Disease who had two muscle biopsies, at age 20 months and 16 years, and from his mother with cardiomyopathy but without clinically apparent skeletal myopathy. In the patient, the number of vacuoles increased over the 14-year interval between biopsies, suggesting that the number of vacuolated fibers increases with age, and correlates with the development of muscle symptoms. In contrast, in the muscle biopsy from the mother there were no vacuoles even though she had decreased LAMP-2.
Matthew R.g. Taylor - One of the best experts on this subject based on the ideXlab platform.
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Danon Disease-Associated LAMP-2 Deficiency Drives Metabolic Signature Indicative of Mitochondrial Aging and Fibrosis in Cardiac Tissue and hiPSC-Derived Cardiomyocytes
Journal of clinical medicine, 2020Co-Authors: Giorgia Del Favero, Luisa Mestroni, Teisha J. Rowland, Eric Adler, Alois Bonifacio, Shanshan Gao, Kunhua Song, Valter Sergo, Orfeo Sbaizero, Matthew R.g. TaylorAbstract:Danon Disease is a severe X-linked disorder caused by deficiency of the lysosome-associated membrane protein-2 (LAMP-2). Clinical manifestations are phenotypically diverse and consist of hypertrophic and dilated cardiomyopathies, skeletal myopathy, retinopathy, and intellectual dysfunction. Here, we investigated the metabolic landscape of Danon Disease by applying a multi-omics approach and combined structural and functional readouts provided by Raman and atomic force microscopy. Using these tools, Danon patient-derived cardiac tissue, primary fibroblasts, and human induced pluripotent stem cells differentiated into cardiomyocytes (hiPSC-CMs) were analyzed. Metabolic profiling indicated LAMP-2 deficiency promoted a switch toward glycolysis accompanied by rerouting of tryptophan metabolism. Cardiomyocytes’ energetic balance and NAD+/NADH ratio appeared to be maintained despite mitochondrial aging. In turn, metabolic adaption was accompanied by a senescence-associated signature. Similarly, Danon fibroblasts appeared more stress prone and less biomechanically compliant. Overall, shaping of both morphology and metabolism contributed to the loss of cardiac biomechanical competence that characterizes the clinical progression of Danon Disease.
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Apical Sparing Strain Pattern in Danon Disease: Insights From a Global Registry.
JACC. Cardiovascular imaging, 2020Co-Authors: Quan M. Bui, Luisa Mestroni, Kimberly N. Hong, Michela Brambatti, Megan Kraushaar, Gary S., Andrew M. Kahn, Chrystelle Bougault, Kylie Boynton, Matthew R.g. TaylorAbstract:Danon Disease (DD) is a rare X-linked autophagic vacuolar myopathy that affects the lysosome-associated membrane protein ( LAMP ) 2 gene and causes severe cardiac manifestations, frequently progressing to end-stage heart failure ([1][1]). The differential diagnosis includes many different Diseases,
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Danon Disease for the cardiologist: case report and review of the literature
Taylor & Francis Group, 2017Co-Authors: Ryan S. D’souza, Luisa Mestroni, Matthew R.g. TaylorAbstract:Danon Disease is a rare, X-linked dominant genetic disorder that is caused by defects in the lysosome-associated membrane protein 2 (LAMP2) gene. It manifests predominantly in young males with a classic triad of cardiomyopathy, skeletal myopathy, and intellectual disability. Death from cardiac Disease is the ultimate cause of demise in many patients if left untreated. Given the rarity of the condition, the natural history is poorly understood. Here, we present a case report on a 14-year-old Hispanic boy with Danon Disease, highlighting major clinical events and diagnostic study findings over a six-year period from age of symptom onset to age of death. He had significant hypertrophic cardiomyopathy (ventricular septal thickness 65 mm) and experienced various arrhythmias during his clinical course including Wolf-Parkinson-White syndrome, non-sustained ventricular tachycardia, and pre-excited atrial fibrillation with a fasciculoventricular anomalous accessory pathway. He had sudden cardiac death from ventricular fibrillation at age 14 and his heart had a weight of 1425 grams at autopsy. We also provide a review of the cardiac Danon Disease literature related to diagnostic and management approaches to aid cardiologists in evaluating and treating cardiac manifestations in Danon Disease patients
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Danon Disease - dysregulation of autophagy in a multisystem disorder with cardiomyopathy.
Journal of cell science, 2016Co-Authors: Teisha J. Rowland, Luisa Mestroni, Mary E. Sweet, Matthew R.g. TaylorAbstract:Danon Disease is a rare, severe X-linked form of cardiomyopathy caused by deficiency of lysosome-associated membrane protein 2 (LAMP-2). Other clinical manifestations include skeletal myopathy, cognitive defects and visual problems. Although individuals with Danon Disease have been clinically described since the early 1980s, the underlying molecular mechanisms involved in pathological progression remain poorly understood. LAMP-2 is known to be involved in autophagy, and a characteristic accumulation of autophagic vacuoles in the affected tissues further supports the idea that autophagy is disrupted in this Disease. The LAMP2 gene is alternatively spliced to form three splice isoforms, which are thought to play different autophagy-related cellular roles. This Commentary explores findings from genetic, histological, functional and tissue expression studies that suggest that the specific loss of the LAMP-2B isoform, which is likely to be involved in macroautophagy, plays a crucial role in causing the Danon phenotype. We also compare findings from mouse and cellular models, which have allowed for further molecular characterization but have also shown phenotypic differences that warrant attention. Overall, there is a need to better functionally characterize the LAMP-2B isoform in order to rationally explore more effective therapeutic options for individuals with Danon Disease.
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Danon Disease Clinical Features, Evaluation, and Management
Circulation. Heart failure, 2014Co-Authors: Ryan S. D'souza, Luisa Mestroni, Dobromir Slavov, Eric Adler, Cecilia Levandowski, Sharon L. Graw, Larry A. Allen, Matthew R.g. TaylorAbstract:Danon Disease is an X-linked dominant skeletal and cardiac muscle disorder with multisystem clinical manifestations. It was first described in boys presenting with cardiomyopathy, skeletal myopathy, and varying degrees of intellectual disability.1 As histological findings of glycogen buildup in muscle tissue similar to those seen in Pompe Disease were noted, the condition was originally considered to be a lysosomal storage Disease and was termed glycogen storage Disease type IIb. In 2000, Nishino et al2 identified the genetic defects in the lysosome-associated membrane protein 2 ( LAMP2 ) gene, encoding the LAMP2 protein. Most Danon Disease mutations lead to an absence of LAMP2 protein expression,2 a situation more problematic in men who are hemizygous for LAMP2 . For reasons not yet fully understood, reduction in LAMP2 disrupts intracytoplasmic trafficking and leads to accumulation of autophagic material and often glycogen in skeletal muscle and cardiac muscle cells (Figure 1).2 Major clinical features include skeletal and cardiac myopathy, cardiac conduction abnormalities, mild intellectual difficulties, and retinal Disease. Men are typically affected earlier and more severely than women. The Disease is unfamiliar to many practitioners, and the majority of published data stem from case reports with a brief clinical review published in 2002.4 Our aim was to perform a systematic review of Danon Disease, provide a comprehensive clinical and molecular update, and propose diagnostic and management guidelines for clinicians and researchers working with patients with Danon Disease. Figure 1. Histological images from skeletal muscle biopsy and endomyocardial biopsy.3 Electron microscopy shows intracytoplasmic vacuoles (arrows) containing autophagic material and glycogen in both ( A ) skeletal muscle (bar 1 μm) and ( B ) endomyocardial tissue biopsy (bar 1 μm). Reprinted from Taylor et al3 with permission of the publisher. Copyright © 2007, Nature Publishing Group. Authorization for this adaptation has been obtained both from …
Victor Escobedo - One of the best experts on this subject based on the ideXlab platform.
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Prevalence and Outcomes of Patients with Wolff-Parkinson-White in Danon Disease: Results of a Retrospective Analysis.
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2020Co-Authors: Mary Brooks, Douglas Darden, Victor Escobedo, Chrystelle Bougalt, K Hong, Eric AdlerAbstract:Danon Disease is a rare X-linked myopathy caused by defects in the lysosome-associated membrane 2 (LAMP2) gene. It is strongly associated with hypertrophic cardiomyopathy as well as Wolff-Parkinson-White (WPW) syndrome, but the prevalence of WPW in Danon is unclear. This study examined the prevalence of WPW and associated outcomes in a cohort of patients with Danon Disease. Records were reviewed for 41 patients with confirmed Danon Disease enrolled in a previously described retrospective registry, 31 of which had at least one electrocardiogram (EKG) on file. EKGs were assessed for the presence of WPW, as well as left and right ventricular hypertrophy (LVH, RVH), or both. WPW was defined as a PR interval ≤ 120 milliseconds, QRS interval ≥120 milliseconds, and delta wave. Charts were reviewed for internal cardiac defibrillator (ICD) placement, heart transplantation, and death. These outcomes were evaluated between patients with and without WPW on EKG using chi-square analysis, with p <0.05 noted to be significant. EKG criteria for LVH, RVH or both was met in 10 of the 11 WPW patients, compared to 9 of the 20 without WPW (p=0.012). ICD devices were present in 9 of the 11 WPW patients, 3 of which were placed for secondary prevention, compared to 9 of the 20 patients without WPW (p=0.119). Six of the 11 WPW patients eventually underwent heart transplant, compared to 4 of the 20 without WPW (p=0.058). Only one death was noted in this cohort, and was determined to not be cardiac related. In a cohort of patients with Danon Disease, approximately one-third had WPW syndrome on EKG. Those with WPW on EKG had higher rates of EKG criteria for LVH, RVH or both and were more likely to require advanced therapies such as ICD placement and cardiac transplant. Larger studies involving WPW in Danon Disease should seek to better characterize these outcomes. Copyright © 2020. Published by Elsevier Inc.
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description of left ventricular strain in Danon Disease insights from a global registry
Journal of the American College of Cardiology, 2020Co-Authors: Quan M. Bui, Kimberly N. Hong, Victor Escobedo, Michela Brambatti, M. Taylor, Megan Kraushaar, Andrew M. Kahn, Chrystelle Bougault, Liz Covarrubias, Eric AdlerAbstract:Danon Disease (DD) is a rare X-linked disorder due to mutations in the Lysosomal Associated Membrane Protein 2 (LAMP-2) gene and causes severe cardiac manifestations. Longitudinal strain (LS) has emerged as a diagnostic and prognostic tool in various cardiomyopathies. A retrospective, international
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WOLFF-PARKINSON-WHITE IN INDIVIDUALS WITH Danon Disease IS A MARKER OF Disease SEVERITY
Journal of the American College of Cardiology, 2020Co-Authors: Mary Brooks, Douglas Darden, Kimberly N. Hong, Victor Escobedo, Michela Brambatti, Chrystelle Bougalt, Eric AdlerAbstract:Danon Disease is a rare X-linked myopathy associated with hypertrophic cardiomyopathy and Wolff-Parkinson-White (WPW) syndrome. The prevalence of WPW in Danon Disease is unclear. This study examined the prevalence of WPW and associated outcomes in a cohort of Danon Disease patients. EKGs of 28
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Prevalence and Outcomes of Patients with Wolff-Parkinson-White in Danon Disease: Results of a Retrospective Analysis.
The Journal of Heart and Lung Transplantation, 2020Co-Authors: Mary Brooks, Douglas Darden, Kimberly N. Hong, Victor Escobedo, Chrystelle Bougalt, Eric AdlerAbstract:Purpose Danon Disease is a rare X-linked myopathy caused by defects in the lysosome-associated membrane 2 (LAMP2) gene. It is strongly associated with hypertrophic cardiomyopathy as well as Wolff-Parkinson-White (WPW) syndrome, but the prevalence of WPW in Danon is unclear. This study examined the prevalence of WPW and associated outcomes in a cohort of patients with Danon Disease. Methods Records were reviewed for 41 patients with confirmed Danon Disease enrolled in a previously described retrospective registry, 31 of which had at least one electrocardiogram (EKG) on file. EKGs were assessed for the presence of WPW, as well as left and right ventricular hypertrophy (LVH, RVH), or both. WPW was defined as a PR interval ≤ 120 milliseconds, QRS interval ≥120 milliseconds, and delta wave. Charts were reviewed for internal cardiac defibrillator (ICD) placement, heart transplantation, and death. These outcomes were evaluated between patients with and without WPW on EKG using chi-square analysis, with p Results EKG criteria for LVH, RVH or both was met in 10 of the 11 WPW patients, compared to 9 of the 20 without WPW (p=0.012). ICD devices were present in 9 of the 11 WPW patients, 3 of which were placed for secondary prevention, compared to 9 of the 20 patients without WPW (p=0.119). Six of the 11 WPW patients eventually underwent heart transplant, compared to 4 of the 20 without WPW (p=0.058). Only one death was noted in this cohort, and was determined to not be cardiac related. Conclusion In a cohort of patients with Danon Disease, approximately one-third had WPW syndrome on EKG. Those with WPW on EKG had higher rates of EKG criteria for LVH, RVH or both and were more likely to require advanced therapies such as ICD placement and cardiac transplant. Larger studies involving WPW in Danon Disease should seek to better characterize these outcomes.
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LONGITUDINAL ECHOCARDIOGRAPHIC FINDINGS OF Danon Disease: INSIGHTS FROM A GLOBAL REGISTRY
Journal of the American College of Cardiology, 2019Co-Authors: Quan M. Bui, Victor Escobedo, Michela Brambatti, Nathan Nguyen, Elizabeth Covarrubias, David Teng, Alessandro Maolo, M. Taylor, Eric AdlerAbstract:Danon Disease (DD) is rare X-linked lysosomal storage disorder with cardiac manifestations of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) mediated by mutations of the LAMP-2 gene. Compared to early presentations in males, females manifest Disease with varying levels of
Kimberly N. Hong - One of the best experts on this subject based on the ideXlab platform.
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Apical Sparing Strain Pattern in Danon Disease: Insights From a Global Registry.
JACC. Cardiovascular imaging, 2020Co-Authors: Quan M. Bui, Luisa Mestroni, Kimberly N. Hong, Michela Brambatti, Megan Kraushaar, Gary S., Andrew M. Kahn, Chrystelle Bougault, Kylie Boynton, Matthew R.g. TaylorAbstract:Danon Disease (DD) is a rare X-linked autophagic vacuolar myopathy that affects the lysosome-associated membrane protein ( LAMP ) 2 gene and causes severe cardiac manifestations, frequently progressing to end-stage heart failure ([1][1]). The differential diagnosis includes many different Diseases,
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description of left ventricular strain in Danon Disease insights from a global registry
Journal of the American College of Cardiology, 2020Co-Authors: Quan M. Bui, Kimberly N. Hong, Victor Escobedo, Michela Brambatti, M. Taylor, Megan Kraushaar, Andrew M. Kahn, Chrystelle Bougault, Liz Covarrubias, Eric AdlerAbstract:Danon Disease (DD) is a rare X-linked disorder due to mutations in the Lysosomal Associated Membrane Protein 2 (LAMP-2) gene and causes severe cardiac manifestations. Longitudinal strain (LS) has emerged as a diagnostic and prognostic tool in various cardiomyopathies. A retrospective, international
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WOLFF-PARKINSON-WHITE IN INDIVIDUALS WITH Danon Disease IS A MARKER OF Disease SEVERITY
Journal of the American College of Cardiology, 2020Co-Authors: Mary Brooks, Douglas Darden, Kimberly N. Hong, Victor Escobedo, Michela Brambatti, Chrystelle Bougalt, Eric AdlerAbstract:Danon Disease is a rare X-linked myopathy associated with hypertrophic cardiomyopathy and Wolff-Parkinson-White (WPW) syndrome. The prevalence of WPW in Danon Disease is unclear. This study examined the prevalence of WPW and associated outcomes in a cohort of Danon Disease patients. EKGs of 28
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Prevalence and Outcomes of Patients with Wolff-Parkinson-White in Danon Disease: Results of a Retrospective Analysis.
The Journal of Heart and Lung Transplantation, 2020Co-Authors: Mary Brooks, Douglas Darden, Kimberly N. Hong, Victor Escobedo, Chrystelle Bougalt, Eric AdlerAbstract:Purpose Danon Disease is a rare X-linked myopathy caused by defects in the lysosome-associated membrane 2 (LAMP2) gene. It is strongly associated with hypertrophic cardiomyopathy as well as Wolff-Parkinson-White (WPW) syndrome, but the prevalence of WPW in Danon is unclear. This study examined the prevalence of WPW and associated outcomes in a cohort of patients with Danon Disease. Methods Records were reviewed for 41 patients with confirmed Danon Disease enrolled in a previously described retrospective registry, 31 of which had at least one electrocardiogram (EKG) on file. EKGs were assessed for the presence of WPW, as well as left and right ventricular hypertrophy (LVH, RVH), or both. WPW was defined as a PR interval ≤ 120 milliseconds, QRS interval ≥120 milliseconds, and delta wave. Charts were reviewed for internal cardiac defibrillator (ICD) placement, heart transplantation, and death. These outcomes were evaluated between patients with and without WPW on EKG using chi-square analysis, with p Results EKG criteria for LVH, RVH or both was met in 10 of the 11 WPW patients, compared to 9 of the 20 without WPW (p=0.012). ICD devices were present in 9 of the 11 WPW patients, 3 of which were placed for secondary prevention, compared to 9 of the 20 patients without WPW (p=0.119). Six of the 11 WPW patients eventually underwent heart transplant, compared to 4 of the 20 without WPW (p=0.058). Only one death was noted in this cohort, and was determined to not be cardiac related. Conclusion In a cohort of patients with Danon Disease, approximately one-third had WPW syndrome on EKG. Those with WPW on EKG had higher rates of EKG criteria for LVH, RVH or both and were more likely to require advanced therapies such as ICD placement and cardiac transplant. Larger studies involving WPW in Danon Disease should seek to better characterize these outcomes.
