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IntroductionDanon disease is an X-linked disorder caused by pathogenic variants in lysosome-associated membrane protein 2 (LAMP2) gene, typically characterized by the triad of hypertrophic cardiomyopathy, myopathy, and intellectual disability. However, many patients may not present the typical presentation, especially in the early stage. Electrocardiogram (ECG) abnormalities can be found in almost all patients, with Wolff–Parkinson–White (WPW) syndrome being the most common. We reported the case of a 51-year-old woman who experienced multiple types of arrhythmias over three decades and was diagnosed with Danon disease late by genetic testing.Case summaryA 51-year-old woman with a 36-year history of intermittent palpitations was admitted due to hemodynamically stable ventricular tachycardia (VT). Her past medical history revealed multiple arrhythmias and ECG abnormalities in her 30s and 40s, including WPW syndrome with paroxysmal supraventricular tachycardia, paroxysmal atrial flutter, atrial fibrillation, ventricular tachycardia, and complete left bundle branch block. She denied any family history of cardiovascular disease or sudden death. Upon arrival, her vital signs were unremarkable. Cardiovascular magnetic resonance (CMR) imaging revealed left ventricular enlargement and late gadolinium enhancement (LGE) in the anterior, inferior, and lateral walls. Subsequent, whole-exome sequencing (WES) gene testing revealed a pathogenic heterozygous variant in LAMP2 gene (c.696T>A; p.Cys232Ter), which confirmed the diagnosis of Danon disease.ConclusionGenetic testing should be considered in patients who display multiple arrhythmias with LV structural abnormalities of unknown etiology for a possible Danon disease.

BackgroundCardiac involvement constitutes the primary cause of mortality in patients with Danon disease (DD). This study aimed to explore the cardiac magnetic resonance (CMR) features and progressions of DD cardiomyopathies in a family with long-term follow-up.MethodsSeven patients (five females and two males), belonging to the same family and afflicted with DD, were enrolled in this study between 2017 and 2022. The cardiac structure, function, strain, tissue characteristics on CMR and their evolutions during follow-up were analyzed.ResultsThree young female patients (3/7, 42.86%) exhibited normal cardiac morphology. Four patients (4/7, 57.14%) displayed left ventricle hypertrophy (LVH), and mostly with septal thickening (3/4, 75%). A single male case (1/7, 14.3%) showed decreased LV ejection fraction (LVEF). Nonetheless, the global LV strain of the four adult patients decreased in different degree. The global strain of adolescent male patients was decreased compared to the age-appropriate female patients. Five patients (5/7, 71.43%) exhibited late gadolinium enhancement (LGE), with proportion ranging from 31.6% to 59.7% (median value 42.7%). The most common LGE location was the LV free wall (5/5, 100%), followed by right ventricle insertion points (4/5, 80%) and intraventricular septum (2/5, 40%). Segmental radial strain (rs = −0.586), circumferential strain (r = 0.589), and longitudinal strain (r = 0.514) were all moderately correlated with the LGE proportions of corresponding segments (P

Danon disease is a rare disease caused by glycogen storage lysosomal disorder. It is related to the pathogenic mutation of the LAMP2 gene. In this case report, we present a patient with a novel pathogenic mutation (c.764_765insGA) with cardiac-only symptoms. Her family members do not carry the same mutation she does, suggesting this is a de novo mutation. Further tests revealed vacuoles and glycogen disposition in the patient's heart tissue and a significant decrease in LAMP2 protein expression. Protein structure remodeling of LAMP2 predicted that the mutant protein has conformational change lacking an important transmembrane domain, subsequently causing protein destabilization.

Danon disease is a rare X-linked dominant genetic disorder that manifests with a clinical triad of cardiomyopathy, skeletal myopathy, and intellectual disability. It is caused by mutations in the lysosome-associated membrane 2 (LAMP2) gene. We report one case of Danon disease and his family members, characterized by ventricular pre-excitation, ventricular hypertrophy, abnormal muscle enzymes, and aberrant liver function. All the patients were confirmed to have Danon disease through genetic screening. Relevant literature was reviewed as a reference for the diagnosis and treatment of the disease.

BackgroundFragmented QRS (f-QRS) complex on the surface ECG is a cardiac conduction abnormality that indicates myocardial scarring. The relationship between the f-QRS complex and cardiac status in patients with Danon disease (DD) remains unclear and will be explored in this study.MethodsPatients with genetically confirmed DD and cardiac magnetic resonance imaging (CMR) examinations were recruited from multiple centers. The number of leads, pattern, score, and segmental distribution of the f-QRS complex were assessed by surface 12-lead ECG. Cardiac status, such as left ventricular (LV) volume, function, and extent of late gadolinium enhancement (LGE), was demonstrated by CMR. The segmental distribution of LGE was also assessed. Correlations between the f-QRS and cardiac status were assessed.ResultsFifteen patients (14 men) with DD who underwent 12-lead ECG and CMR imaging were included. The f-QRS complex was documented in all patients (n = 15, 100%). Three patterns of f-QRS were found, with the notched R/S pattern (74%) being the most common, followed by fragmented QRS (16%) and various RSR' (11%). The fragmented QRS pattern showed an association with a higher level of myocardial fibrosis (LGE > 35%). The burden of f-QRS in each patient was assessed by the number of leads with f-QRS (median 7, range 2–12) and the f-QRS score (median 9, range 2–33). In the correlation analysis, the f-QRS score was positively correlated with LGE% (r = 0.726, p = 0.002), negatively correlated with LV ejection function (LVEF; r = −0.617, p = 0.014) as evaluated by CMR. In the local distribution, f-QRS score and LGE% were both predominant in the LV free wall but did not correlate well among the anterior, lateral, and inferior segments.ConclusionIn this DD cohort, the quantitative f-QRS was correlated well with myocardial fibrosis burden and LV dysfunction in general. This finding suggests that f-QRS can be used as a simple screening tool to assess cardiac status in patients with DD.

Danon disease (DD) is a rare glycogen storage lysosomal disorder caused by mutations in the LAMP2 gene. Patients with DD are usually characterized clinically by severe multisystem syndromes. We describe a specific family with a novel pathogenic splice-altering mutation in the LAMP2 gene (c.741+2T>C) with cardiac-only symptoms (frequent ventricular tachycardia, intraventricular block, and hypertrophic cardiomyopathy). Minigene assays were used to evaluate the consequence of the splice-site mutation in the LAMP2 gene. The results showed that the c.741+2T>C mutation led to extra 6-bp preservation of intron 5 at the junction between exons 5 and 6 during transcriptional processing of the mRNA, which creates a stop codon and truncated the LAMP2 protein to 248-amino-acid residues. The mutant LAMP2 protein was predicted to have a conformational change, lacks the important transmembrane domain, and subsequent protein destabilization.

Danon disease (DD) is a monogenic lysosomal storage disorder characterized by cardiomyopathy, skeletal myopathy, and variable degrees of intellectual disability. It is caused by a deficiency of lysosomal-associated membrane protein 2 (LAMP2). Two unrelated boys who presented with severe hypertrophic cardiomyopathy and elevated levels of liver enzymes, and were diagnosed with Danon disease at a very young age, were investigated. One boy was diagnosed at 4 months old and died soon after; his mother also died of hypertrophic cardiomyopathy shortly after his birth. Another developed hypertrophic cardiomyopathy at 3 months old but reported no significant cardiovascular symptoms during more than 5 years follow-up. Genetic screening found compound variants of LAMP2 and MYH7 in both of them. This report highlights the clinical heterogeneity in DD. The timely identification of LAMP2 mutation plays a critical role in their treatment and family counseling.

Danon disease (DD) is a monogenic lysosomal storage disorder characterized by cardiomyopathy, skeletal myopathy, and variable degrees of intellectual disability. It is caused by a deficiency of lysosomal-associated membrane protein 2 (LAMP2). Two unrelated boys who presented with severe hypertrophic cardiomyopathy and elevated levels of liver enzymes, and were diagnosed with Danon disease at a very young age, were investigated. One boy was diagnosed at 4 months old and died soon after; his mother also died of hypertrophic cardiomyopathy shortly after his birth. Another developed hypertrophic cardiomyopathy at 3 months old but reported no significant cardiovascular symptoms during more than 5 years follow-up. Genetic screening found compound variants of LAMP2 and MYH7 in both of them. This report highlights the clinical heterogeneity in DD. The timely identification of LAMP2 mutation plays a critical role in their treatment and family counseling. [ABSTRACT FROM AUTHOR]