Cardiac Transplantation in Danon Disease

Hong, Kimberly N.; Battikha, Carol E.; John, Sonya; Lin, Andrew; Bui, Quan M.; Brambatti, Michela; Storm, Garrett; Boynton, Kylie; Medina-Hernandez, Danielle; García‐Álvarez, Ana; Castel, Á.; García-Guereta, Luis; Díez-López, Carles; Pérez-Gómez, Laura; Miani, Daniela; Symanski, John D.; Taylor, Matthew R.G.; García‐Pavía, Pablo; Adler, Emanuel

doi:10.1016/j.cardfail.2021.11.007

Cited by 7 publications

(4 citation statements)

References 6 publications

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“…A large multicentre study on 38 transplanted patients with DD (19 for each sex) reported a 5-year survival rate of 87.1% for both sexes. 18 After 7 years of follow-up, our transplanted patient is alive with optimal quality of life.…”

Section: Discussionmentioning

confidence: 86%

Danon disease in a Sardinian family: different aspects of the same mutation—a case report

Pasqualucci

Maiani

Perra

et al. 2023

European Heart Journal - Case Reports

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Background Danon disease (DD) is a rare X-linked disorder due to mutations in the lysosome-associated membrane protein 2 (LAMP-2) gene. It is characterized by a clinical triad of hypertrophic cardiomyopathy (HCM), skeletal myopathy and variable degree of intellectual disability. Case summary In this case series we describe a mother and her son affected by DD, highlighting consistent clinical severity despite the expected variability related to gender. The mother (case 1) presented isolated cardiac involvement, with an arrhythmogenic phenotype which evolved to severe heart failure requiring heart transplantation. DD was diagnosed 1 year after this event. Her son (case 2) showed an earlier age onset of symptoms with complete atrio-ventricular block and fast progression of cardiac disease. Diagnosis was established 2 years after clinical presentation. He is currently listed for heart transplantation. Conclusion In both our patients the diagnostic delay was extremely long and could have been avoided by emphasizing the relevant clinical red flags. Patients affected by DD may present clinical heterogeneity in terms of natural history, age of onset, cardiac and extra-cardiac involvement even in the same family. Early diagnosis, that phenotypic sex differences may impact, is a crucial factor in managing patients with DD. Considering the rapid progression of cardiac disease and the poor prognosis, an early diagnosis is important and close surveillance should be mandatory during follow-up.

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Section: Discussionmentioning

confidence: 86%

Danon disease in a Sardinian family: different aspects of the same mutation—a case report

Pasqualucci

Maiani

Perra

et al. 2023

European Heart Journal - Case Reports

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“…Similar to our previously published data on DD patients who underwent transplantation, while there was a trend towards HF outcome occurring at an earlier age in males compared to females, this did not reach statistical significance. 4 This is likely due to there being a distinct subset of females who experience a HF outcome at an earlier age in the absence of advanced heart failure therapies. In this study group, when female patients who reached HF outcome were stratified into early (less than 26 years old) and late (greater than or equal to 26 years old) HF outcome groups, 2 distinct age groups were noted (p=0.002).…”

Section: Heart Failure Outcomesmentioning

confidence: 99%

“…DD in males is typically lethal without cardiac transplantation, and while disease severity is variable in females, there is a subset of females who require cardiac transplantation at similar ages to males. [2][3][4][5] As an X-linked disorder, disease course varies by sex, with males typically developing extracardiac symptoms early in childhood. Cardiac manifestations present soon after and reach end-stage in males by the second or third decade of life.…”

Section: Introductionmentioning

confidence: 99%

An International Longitudinal Natural History Study of Danon Disease Patients: Unique Cardiac Trajectories Identified Based on Sex and Heart Failure Outcomes

Hong,

Eshraghian,

Khedro

et al. 2024

Preprint

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Introduction: Danon disease (DD) is a rare X-linked dominant cardioskeletal myopathy caused by mutations in the lysosome-associated membrane protein-2 gene. Though the severe morbidity of disease in males is well established, longitudinal studies describing the trajectory of cardiovascular disease in both sexes have not been performed. Herein we performed an analysis using the International Danon Disease Registry, a retrospective dataset that includes longitudinal data from a cohort of males and females with DD. Methods: Data were from the International Danon Disease Registry and includes patients from 2005 to 2022. Records were obtained from the first episode of care to the date of enrollment and included demographics, clinical characteristics, echocardiographic and laboratory values, and outcomes. The primary outcome in this study was a heart failure (HF) composite defined as either transplant (TXP), left ventricular assist device (LVAD) or death. Results: The analysis included 116 DD patients: female (n=64, 55%) and male (n=52, 45%). Median age of diagnosis for the entire cohort was 15.2 years (10.0-25.2 years), and 21.9 years (15.0-34.9 years) and 12.4 years (7.1-15.6 years) for females and males respectively. The incidence of HF outcome was higher in males compared to females (p<0.001). Regarding trends in echocardiographic parameters over time, LVEF decreased and LVEDD increased regardless of sex and HF outcome, however, rate of change was increased in patients who experienced a HF outcome in both sexes. Increasing LV mass occurs in males but not females. Consistent with this, LV wall hypertrophy continues in males who have not yet experienced a HF outcome and stabilizes prior to HF outcome, while females have progressive LV thinning regardless of HF outcome. Analyses stratified by age of HF outcome in females found two distinct groups of females, one who experienced HF outcome prior to 26 years of age and another after. Conclusions: In this largest longitudinal natural history study of DD to date, we confirmed that males present on average a decade earlier and demonstrate more progressive cardiac hypertrophy and heart failure than females. Of note, there may be a subset of females who are phenotypically similar to males with profound LV hypertrophy that appears to stabilize or regress prior to HF outcome. Correlations between structural changes including LV hypertrophy, dilation and dysfunction and disease progression may allow for risk stratification of Danon patients and refinement of treatment algorithms while also informing therapeutic trial design.

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“…A systematic cognitive and psychiatric assessment of males and females with Danon disease revealed that 69.2% of participants met the criteria for at least one psychiatric illness and 53.8% had two or more psychiatric disorders [ 7 ]. Individuals with Danon disease may also display ocular pathology, particularly retinal disease [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Dilated Cardiomyopathy and Systolic Heart Failure in a Female Patient With Danon Disease

Stack-Pyle¹,

Shah²,

Stack³

et al. 2022

Cureus

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Danon disease commonly manifests as isolated hypertrophic cardiomyopathy in female patients. The diagnosis is easily missed as it is rare and its pathophysiology is poorly understood. Without early diagnosis and treatment with heart transplantation, cardiomyopathy may progress to heart failure. We present the case of an adolescent female with Danon disease who presented with heart failure with reduced ejection fraction secondary to dilated cardiomyopathy. Her original presentation included a six-month history of shortness of breath, vomiting, and abdominal pain. Further workup revealed pelvic ascites and dilated cardiomyopathy with signs of heart failure. Genetic testing confirmed the diagnosis, revealing a previously undocumented amino acid substitution in the lysosomal-associated membrane protein-2 (LAMP2) gene. The patient received a heart transplant which led to an improvement in her symptoms. The patient's unique symptomatology illustrates the importance of early cardiac monitoring and transplantation if Danon disease is suspected. This uncommon presentation of dilated cardiomyopathy followed by psychiatric impairment, developmental disability, and unique LAMP2 genetic substitution provides a rare phenotype of Danon disease.

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Cardiac Transplantation in Danon Disease

Cited by 7 publications

References 6 publications

Danon disease in a Sardinian family: different aspects of the same mutation—a case report

Danon disease in a Sardinian family: different aspects of the same mutation—a case report

An International Longitudinal Natural History Study of Danon Disease Patients: Unique Cardiac Trajectories Identified Based on Sex and Heart Failure Outcomes

Dilated Cardiomyopathy and Systolic Heart Failure in a Female Patient With Danon Disease

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