Name: RP-A501 (AAV9.LAMP2B) in Danon disease: Long-term morbidity
Published: 2026-10-08T12:19:25-04:00

Progression to systolic dysfunction and end-stage heart failure

“Typically, owing to cardiomyocyte death and progressive fibrosis, the hypertrophic heart becomes hypokinetic, followed by wall thinning and possible dilation.” (opens the source at this quote in a new tab)

“All 7 patients developed marked LV systolic dysfunction (ejection fraction, 20–35%; mean 25±7), associated with LV cavity dilatation in 4 and enlargement in 2 others over the follow-up period.” (opens the source at this quote in a new tab)

“All patients presented phenotypically with hypertrophic cardiomyopathy and later developed systolic dysfunction.” (opens the source at this quote in a new tab)
“Three patients required cardiac transplantation (ages 15, 27, and 42). Of the two deaths in this group, both were in women.” (opens the source at this quote in a new tab)

“During this period, 48% of these DD patients were admitted for heart failure (50% of male patients and 47% of female patients)” (opens the source at this quote in a new tab)

Myocardial fibrosis on cardiac magnetic resonance

“Eleven DD had gadolinium-based contrast administered. Of these, 3 showed no LGE. All remaining (8, 73%) had various LGE patterns and distributions but LGE was always sparing the mid septum.” (opens the source at this quote in a new tab)

“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%).” (opens the source at this quote in a new tab)

“Cardiac MR revealed extensive LGE (21.9% ± 11.4%, diffuse free-wall involvement), elevated extracellular volume (ECV) (ECV: 38% ± 12%), and significantly prolonged T1/T2 values” (opens the source at this quote in a new tab)

Implanted cardiac devices and catheter ablation: frequency in cohorts

“Within patients who received a CIED, 2 male patients (3.8%) were implanted with pacemakers alone; the remaining patients were implanted with an automatic implantable cardioverter defibrillator, of which 5.2% (n=2) were for secondary prevention.” (opens the source at this quote in a new tab)

“A total of 38 (67%) patients received an implantable device (Table 2): permanent pacemaker, implantable cardiac defibrillator (ICD) or cardiac resynchronization therapy with an ICD (CRT-D).” (opens the source at this quote in a new tab)
“Eight were implanted for a secondary prevention after sustained ventricular tachycardia (n=4) or resuscitation for cardiac arrest due to ventricular fibrillation (n=4).” (opens the source at this quote in a new tab)

“In the series, 11 patients (41%; 8 female and 3 male) received an implantable cardioverter defibrillator (ICD).” (opens the source at this quote in a new tab)

“Cardiac ablation procedures were performed on one half of men and one third of women. Implantable defibrillators were placed in 41% and 31% of men and women, respectively; data on rates of appropriate discharge could not be ascertained.” (opens the source at this quote in a new tab)

“Over median follow-up of 842 days (interquartile range 138-1678), 11 patients (85%) had ICD placement, and 6 (46.1%) underwent heart transplantation.” (opens the source at this quote in a new tab)

Stroke and thromboembolism

“Embolic strokes from intracardiac thrombi, in the setting of depressed left ventricular function, apical aneurysms, or atrial fibrillation or flutter can also occur.” (opens the source at this quote in a new tab)

“Two female patients had cerebral infarction. One female patient had young-onset stroke due to diffuse narrowing of the cerebral arteries without atherosclerosis, while the other had minor right cerebral infarction occurring after the LVAD operation.” (opens the source at this quote in a new tab)
“Cerebral infarction is quite a rare complication of Danon disease.” (opens the source at this quote in a new tab)

“Atrial fibrillation is frequently observed in these patients and may be associated with thromboembolic events in the young, while sustained ventricular arrhythmias occur less frequently than previously reported.” (opens the source at this quote in a new tab)

“We present a 17-year-old female adolescent with Danon disease who developed TIA and ischemic stroke in association with an LV apical thrombus.” (opens the source at this quote in a new tab)
“Our patient never developed congestive heart failure, atrial fibrillation, or LV aneurysm.” (opens the source at this quote in a new tab)

Skeletal myopathy: course over time and ambulation

“Symptomatic male patients showed proximal limb weakness, which was very slowly progressive or stable.” (opens the source at this quote in a new tab)

“Weakness is seldom debilitating and patients usually retain the ability to walk as adults.” (opens the source at this quote in a new tab)

“Out of the seven patients who had follow-up data, four (57%, n = 4) had no changes over 6-, 12-, 24-, and 36-month follow-ups.” (opens the source at this quote in a new tab)
“After a mean follow-up time of 23.3 months, four patients walked shorter distances (57%, n = 4). The mean distance at last follow-up was 405.9 ± 136.1 m, with an average paired difference of -25.9 m.” (opens the source at this quote in a new tab)

Retinal disease: change with age

“The severity of retinal pathology increased with age, resulting in marked cone-rod involvement overtime.” (opens the source at this quote in a new tab)

“Retinal manifestations are the most common ophthalmic finding in Danon disease and can lead to significant vision loss.” (opens the source at this quote in a new tab)

“Hyperfundus autofluorescence and hypofundus autofluorescence changes became more confluent and florid with increasing age of female patients. Goldmann visual field testing showed constriction of the central field.” (opens the source at this quote in a new tab)

Cognitive impairment: course over time

“In addition, their learning disturbance did not progress, and their condition remained stable” (opens the source at this quote in a new tab)

“To present a unique case involving a 31-year-old male with Danon disease (diagnosed at 14) who received cardiac transplant and subsequent cardiac re-transplant.” (opens the source at this quote in a new tab)
“A consistent pattern of higher level cognitive impairment from childhood through adulthood was found.” (opens the source at this quote in a new tab)

After heart transplantation: skeletal muscle weakness and other extracardiac events

“Despite the presence of extracardiac involvement including skeletal muscle disease, which may limit rehabilitation, post-transplantation outcomes are good.” (opens the source at this quote in a new tab)

“Males had higher pretransplant aspartate aminotransferase, alanine aminotransferase and creatine phosphokinase levels than females (P < 0.001). There were 2 deaths in the entire cohort and 2 retransplants.” (opens the source at this quote in a new tab)

“In both patients, the post-transplant course was complicated by profound skeletal muscle weakness that resolved with corticosteroid withdrawal.” (opens the source at this quote in a new tab)

“We report a case of late-progressive, profound weakness after heart transplantation for noncompaction cardiomyopathy which required prolonged mechanical ventilation. The patient's muscle strength recovered completely after prolonged rehabilitation.” (opens the source at this quote in a new tab)

“This case describes an uncommon acute complication of diffuse thrombotic angiopathy and associated aHUS/TTP in an 11-year-old girl with Danon disease who underwent orthotopic heart transplant.” (opens the source at this quote in a new tab)

“Another 38-year-old male patient transplanted 15 years previously developed depression, cognitive decline with dementing features, and severe paranoia necessitating psychiatric hospitalization (un-published data). It is unclear currently if either psychiatric episode was related to Danon disease.” (opens the source at this quote in a new tab)

Late outcomes in females

“Danon disease presents earlier in men than in women and runs a malignant course in both sexes, due to cardiac complications.” (opens the source at this quote in a new tab)

“Female carriers with LAMP2 mutations most often present with late onset cardiomyopathy and slow disease progress; however, there are unusual cases that emerge early and show a more severe disease course.” (opens the source at this quote in a new tab)

“As DD female patients regularly progress into advanced heart failure (AHF) aged 20–40 years, their early identification is critical to improve patient survival and facilitate genetic counselling.” (opens the source at this quote in a new tab)
“The total prevalence of DD in this cohort was 12%.” (opens the source at this quote in a new tab)

“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.” (opens the source at this quote in a new tab)

“Wolff-Parkinson-White pattern with atrioventricular block was detected in 2 of 6 women. Four had successful pregnancies without symptoms of heart failure.” (opens the source at this quote in a new tab)

“Males predominantly developed hypertrophic cardiomyopathy (HCM: 73.3%), whereas females universally exhibited dilated cardiomyopathy (DCM: 88.9%) with preserved septal thickness. Ventricular arrhythmias occurred in all females (100% vs. 73.3% in males). Females showed significantly worse left ventricular ejection fraction (LVEF: 37.0% ± 14.0% vs. 49.9% ± 17.9%).” (opens the source at this quote in a new tab)