Cardiac Phenotype Characterization at MRI in Patients with Danon Disease: A Retrospective Multicenter Case Series.

Danon disease (DD) is a rare X-chromosome-linked dominant lysosomal glycogen storage disease. Its features have seldom been reported by using cardiac MRI. This case series aimed to evaluate cardiac features of DD on the basis of MRI observations from five centers in China. From January 2010 to May 2019, 16 patients with DD (13 male patients [81%]; median age, 19 years; age range, 14-44 years) underwent MRI. The most frequent DD cardiomyopathy manifestation was symmetric hypertrophy cardiomyopathy (HCM) phenotype (nine of 16; 56%), followed by asymmetric HCM phenotype (six of 16; 38%) and dilated cardiomyopathy phenotype (one of 16; 6%). The characteristic late gadolinium enhancement features included midbasal septum sparing (14 of 16; 88%) and apex involvement (16 of 16; 100%) with a base-to-apex increasing tendency, free wall involvement (15 of 16; 94%), and extensive subendocardium involvement (14 of 16; 88%). Abnormal T2 signal (seven of 16; 44%) and resting perfusion defect (14 of 16; 88%) were not uncommon in patients with DD. Furthermore, the cardiac MRI features of DD cohort in this study were compared with those of DD in previous literature and with genetically confirmed sarcomeric HCM.

Progression of Danon disease with medical imaging: two case reports.

Danon disease is a rare X-linked dominant genetic disorder caused by loss-of-function mutations in the lysosome-associated membrane protein 2 gene. Progression of Danon disease is unknown because of its rare incidence in a diverse ethnic population. We report longitudinal data from two patients who were diagnosed with Danon disease by a genetic test. The evaluation protocol included electrocardiographic monitoring, echocardiography, and magnetic resonance imaging. Progression of hypertrophic cardiomyopathy to dilated cardiomyopathy was observed in the first patient. He died from sudden cardiac arrest. The second patient is currently suffering from hypertrophic cardiomyopathy. Development of the hypertrophic phase progressing into the dilated phase in Danon disease may provide useful information for early identification and clinical decisions in patients with this disease.

Glycogen storage cardiomyopathy (PRKAG2): diagnostic findings of standard and advanced echocardiography techniques.

AIMS: Describe the findings obtained using standard echocardiography (Echo) and deformation indices (2D and 3D speckle tracking strain) in patients (Pts) with PRKAG2 cardiomyopathy. Seek to identify any peculiar characteristics and possible strain patterns that may distinguish this condition from other causes of left ventricular hypertrophy (LVH). METHODS AND RESULTS: Thirty Pts with genetically proven PRKAG2 (R302Q and H401Q), 16 (53.3%) male, mean age 39.1± 15.4 years old, were examined using standard, speckle tracking (STE), and 3D Echo. Pacemaker (PM) had been implanted in 12 (40%) Pts with a mean age of 38.1 ± 13 years. Hypertrophy was found in varying degrees in 18 (86%) Pts. Seven Pts (24%) presented 3D ejection fraction (EF) below normal limits. Diastolic function was abnormal in 17 (63%) Pts. Global longitudinal strain (GLS) on 2D measured -16.4% ± 5.3%. GLS measured -13.2% ± 4.8%, global radial strain 40.8% ± 13.8%, global circumferential strain (GCS) -16.1% ± 4.4%, and global area strain -26.1% ± 6.7% by 3D Echo offline analyses. Pts with PM presented lower EF and GCS compared with those without PM. EF/GLS measured 3.65 ± 1.00. In the bull's eye map, a strain pattern similar to stripes in 18 (60%) Pts was identified, which might be a differentiating signal among LVH. CONCLUSION: Echocardiography is a valuable tool in detecting diffuse and focal myocardial abnormalities in PRKAG2 cardiomyopathy. The deformation indices are especially revealing because they may help distinguish this rare infiltrative disease, thereby favouring early diagnosis, enhanced treatment, and improved outcome.

Clinical utility of genetic testing in the early diagnosis of Danon disease mimicking hypertrophic cardiomyopathy: a case report.

BACKGROUND: Danon disease (OMIM 300257) is an X-linked lysosomal storage disorder, characterized by hypertrophic cardiomyopathy (HCM), skeletal myopathy, variable intellectual disability, and other minor clinical features. This condition accounts for ~ 4% of HCM patients, with a more severe and early onset phenotype in males, causing sudden cardiac death (SCD) in the first three decades of life. Genetic alterations in the LAMP2 gene are the main cause of this inherited fatal condition. Up to date, more than 100 different pathogenic variants have been reported in the literature. However, the majority of cases are misdiagnosed as HCM or have a delay in the diagnosis. CASE PRESENTATION: Here, we describe a young boy with an early diagnosis of HCM. After 2 episodes of ventricular fibrillation within 2 years, genetic testing identified a novel LAMP2 pathogenic variant. Subsequently, further clinical evaluations showing muscle weakness and mild intellectual disability confirmed the diagnosis of Danon disease. CONCLUSIONS: This report highlights the role of genetic testing in the rapid diagnosis of Danon disease, underscoring the need to routinely consider the inclusion of LAMP2 gene in the genetic screening for HCM, since an early diagnosis of Danon disease in patients with a phenotype mimicking HCM is essential to plan appropriate treatment, ie cardiac transplantation.

Malignant cardiac phenotypic expression of Danon disease (LAMP2 cardiomyopathy).

INTRODUCTION: Danon disease is an X-linked lysosomal condition that causes a deficiency of lysosome-associated membrane protein 2 (LAMP2) gene. It is characterized clinically by a triad of skeletal myopathy, cardiomyopathy, and intellectual disability. METHODS: We examined clinical, echocardiographic, and genetic data on 5 patients with Danon disease, highlighting their clinical course and outcomes. RESULTS: All patients presented phenotypically with hypertrophic cardiomyopathy and later developed systolic dysfunction. The mean age at diagnosis was 19years (11-31years). All patients had diastolic dysfunction (mean e' of 5cm/s [3.5-6cm/s], mean E/e' of 17 [15-21]). Three patients required cardiac transplantation (ages 15, 27, and 42). Of the two deaths in this group, both were in women. CONCLUSION: We highlight the aggressive cardiac phenotype of Danon disease in our clinical experience with rapid progression to end-stage cardiomyopathy; this progression occurred in both men and women. A timely diagnosis and an early referral for cardiac transplantation is crucial for improved outcomes.