Evicenter
P&T meetings

RP-A501 (AAV9.LAMP2B)

Danon disease

Regulatory submission
BLA planned for late 2028
Last updated
300 sources

Product information and disease descriptionPlace of product in therapyDisease descriptionEpidemiology

Prevalence of Danon disease

28 evidence topics · 31 sources

General population prevalence: stated as unknown in reference sources

“Danon disease is rare; measures of the general population prevalence are not known.” (opens the source at this quote in a new tab)

“Danon disease is a rare condition, but the exact prevalence is unknown.” (opens the source at this quote in a new tab)

“The prevalence of Danon disease is unknown and as cases have been described around the world it can likely affect any ethnic group.” (opens the source at this quote in a new tab)

Orphanet prevalence class and number of described families

“Prevalence: <1 / 1 000 000” (opens the source at this quote in a new tab)

“More than 100 families have been described in the literature so far.” (opens the source at this quote in a new tab)

Published cases: counts from literature reviews

“Among 83 manuscripts in MEDLINE and EMBASE on DD cases published until October 2017, we identified 146 patients with positive genetic testing for DD or positive muscle biopsy in a relative of a genetically diagnosed proband.” (opens the source at this quote in a new tab)

“We surveyed over 500 Danon disease patients reported in the literature from the first description to the present, in order to summarize the clinical, pathological and molecular data and treatment perspectives.” (opens the source at this quote in a new tab)

“It is an extremely rare disease, with about 100 families found so far in the world” (opens the source at this quote in a new tab)

Frequency in hypertrophic cardiomyopathy: range cited by the consensus statement and GeneReviews

“The estimated prevalence of individuals with hypertrophic cardiomyopathy who have an identifiable likely pathogenic or pathogenic variant in the LAMP2 gene is 1% to 4%.” (opens the source at this quote in a new tab)

“Notably, the prevalence of Danon disease increases to 17% in individuals with both hypertrophic cardiomyopathy and pre-excitation.” (opens the source at this quote in a new tab)

“Among individuals with hypertrophic cardiomyopathy (which has an overall prevalence of ~1:500 persons) the prevalence of those with a pathogenic LAMP2 variant has been reported as 1%-4%” (opens the source at this quote in a new tab)

Frequency in hypertrophic cardiomyopathy: under 1% in the 2022 expert consensus table of implicated genes
GeneLocusSyndromeProtein (functional effect)FrequencyClinGen classification
LAMP2“Xq24”“Danon disease”“Loss-of-function”“<1%”“Definite”
Frequency in a French hypertrophic cardiomyopathy cohort: 2 of 197 index cases

“A population of 197 index cases was considered; 124 were subsequently excluded because of a mutation in sarcomeric genes and 23 because of autosomal dominant inheritance.” (opens the source at this quote in a new tab)

“The prevalence was therefore 1% of the total population (two of 197) or 4% of enrolled index cases (two of 50).” (opens the source at this quote in a new tab)

“Interestingly, Danon’s disease was responsible for half of the cases (two of four) with HCM and clinical skeletal myopathy but was not involved in isolated HCM (none of 41).” (opens the source at this quote in a new tab)

Frequency in an unselected pediatric hypertrophic cardiomyopathy cohort, United States: 2 of 50 probands

“In this study we investigated the frequency of LAMP2 mutations in an unselected pediatric HCM population.” (opens the source at this quote in a new tab)

“LAMP2 was amplified from genomic DNA isolated from peripheral lymphocytes of 50 patients diagnosed with HCM and analyzed by direct DNA sequencing. In 2 of the 50 probands (4%), nonsense mutations were identified.” (opens the source at this quote in a new tab)

Frequency in a pediatric cardiomyopathy cohort, China: 4 of 64 probands with hypertrophic cardiomyopathy

“In this study, we developed a targeted panel-based next generation sequencing pipeline to identify mutations by sequencing of selected candidate genes in 136 pediatric patients with either hypertrophic cardiomyopathy (HC) or idiopathic dilated cardiomyopathy (IDC).” (opens the source at this quote in a new tab)

“This led to the identification of lysosome-associated membrane protein 2 (LAMP2) mutations in 4 of the 64 (6%) probands with HC, including 3 novel nonsense mutations (p.Q240X, p.S250X, and p.G22X). No LAMP2 mutation was detected in the other 72 probands with IDC.” (opens the source at this quote in a new tab)

Frequency in hypertrophic cardiomyopathy with and without pre-excitation, United States: three series

“Genetic analyses performed in 75 consecutive unrelated patients with hypertrophic cardiomyopathy detected 40 sarcomere-protein mutations.” (opens the source at this quote in a new tab)

“Gene defects causing Fabry's disease (GLA) and Pompe's disease (GAA) were not found, but two LAMP2 and one PRKAG2 mutations were identified in probands with prominent hypertrophy and electrophysiological abnormalities.” (opens the source at this quote in a new tab)

“Genetic analyses of 20 subjects with massive hypertrophy (left ventricular wall thickness, > or =30 mm) but without electrophysiological abnormalities revealed mutations in neither LAMP2 nor PRKAG2.” (opens the source at this quote in a new tab)

“Genetic analyses of 24 subjects with increased left ventricular wall thickness and electrocardiograms suggesting ventricular preexcitation revealed four LAMP2 and seven PRKAG2 mutations.” (opens the source at this quote in a new tab)

Frequency in unexplained left ventricular hypertrophy with pre-excitation, China: 3 of 10 participants

“Electrocardiographic preexcitation was identified in 10 of 197 patients with unexplained LVH in whom genetic testing was performed using next-generation sequencing.” (opens the source at this quote in a new tab)

“Three (3/10, 30%) patients with Danon disease were found in association with different mutations in the gene of lysosome-associated membrane protein 2 (LAMP2).” (opens the source at this quote in a new tab)

Frequency in concentric left ventricular hypertrophy undergoing endomyocardial biopsy, China: 3 of 50 participants

“A total of 50 patients with concentric LVH underwent EMB from January 2008 to December 2010. Cardiac amyloidosis was diagnosed in 14 patients; genetic analysis of lysosome-associated membrane protein 2 (LAMP2) was done in the remaining 36 patients.” (opens the source at this quote in a new tab)

“The prevalence of Danon disease was seen in 6% (3 of 50) of unselected concentric LVH patients who underwent EMB, or 8% (3 of 36) after excluding cardiac amyloidosis through EMB.” (opens the source at this quote in a new tab)

Frequency in women under 40 years with advanced heart failure, Czech Republic: 12% of 60 participants

“In this study, we evaluated the prevalence of DD among female patients with non-ischemic cardiomyopathy, who reached AHF and were younger than 40 years.” (opens the source at this quote in a new tab)

“The study cohort comprised 60 female patients: 47 (78%) heart transplant recipients, 2 (3%) patients treated with ventricular assist device, and 11 (18%) patients undergoing pre-transplant assessment.” (opens the source at this quote in a new tab)

“Aetiology of the cardiomyopathy was known in 15 patients (including two DD patients).” (opens the source at this quote in a new tab)

“Five additional female DD patients (two with different novel LAMP2 mutations) were identified by FC. The total prevalence of DD in this cohort was 12%.” (opens the source at this quote in a new tab)

Frequency in a global cohort with unexplained increased left ventricular wall thickness: LAMP2 variants in 4 participants among 2,068 tested

“This study included 2068 patients with unexplained increased LVWT enrolled at cardiological clinics across 22 countries/regions between 2020 and 2022.” (opens the source at this quote in a new tab)

“Among the 2068 patients, 453 patients were positive for pathogenic/likely pathogenic variants (21.9%).” (opens the source at this quote in a new tab)

GeneMaleFemaleTotal% of participants with a pathogenic or likely pathogenic variantMean age (years)
LAMP2“1”“3”“4”“0.9”“26.75 ± 5.91”
Frequency in a hypertrophic cardiomyopathy cohort, Türkiye: 392 participants, with 2 LAMP2 cases in the results and 1 in the discussion of the same article

“A total of 392 patients with hypertrophic cardiomyopathy were included in this nationwide multicenter study conducted at 23 centers across Türkiye.” (opens the source at this quote in a new tab)

“These 69 samples with LP or P variants involved MYBPC3 (n = 30), MYH7 (n = 28), DES (n = 4), GLA (n = 2), TPM1 (n = 2), LAMP2 (n = 2), TNNT2 (n = 1), and TNNI3 (n = 1) genes” (opens the source at this quote in a new tab)

“Notably, the 69 positive samples with LP or P variants in our study involved MYBPC3 (n = 31) and MYH7 (n = 28) genes in the majority of cases, while GLA (n = 2), DES (n = 3), and LAMP2 (n = 1) were the genes involved only in 6 cases.” (opens the source at this quote in a new tab)

Frequency in selected populations: range across studies

“Although Danon disease is considered as a rare entity with unknown prevalence in general population, but cases have been frequently reported in 4% to 33% of selected populations” (opens the source at this quote in a new tab)

“In another selected population, three Danon disease patients (33%) were present in a subgroup of nine male patients with both vacuolar myopathy on muscle biopsy and hypertrophic cardiomyopathy.” (opens the source at this quote in a new tab)

United States estimate extrapolated from hypertrophic cardiomyopathy prevalence: 10,000 to 25,000 cases in the 2022 code proposal

“The true prevalence of Danon disease is not known.” (opens the source at this quote in a new tab)

“A crude estimate of prevalence can be based on extrapolation from studies of pediatric and adult hypertrophic cardiomyopathy (for which there is an overall prevalence of approximately 1:500 in the overall population); in these series, LAMP2 pathogenic variants have been identified as underlying approximately 1% - 4% of hypertrophic cardiomyopathy cases” (opens the source at this quote in a new tab)

“These data yield an estimate of 10,000 – 25,000 total cases in the US.” (opens the source at this quote in a new tab)

“Danon disease is GSD type IIB, involving the gene LAMP2, X-linked dominant, prevalence 1:12,000 – 1:50,000 individuals.” (opens the source at this quote in a new tab)

United States estimate from a hypertrophic cardiomyopathy-based model: method and stated limits, 2025 congress abstract

“To address this, we developed a methodology leveraging the established epidemiology of HCM and published rates of LAMP2 mutations in genetically characterized HCM populations to estimate DD prevalence in the U.S.” (opens the source at this quote in a new tab)

“A weighted average mutation rate was calculated from these datasets and applied to the estimated U.S. HCM population.” (opens the source at this quote in a new tab)

“The application of literature-based LAMP2 positivity rates to the estimated HCM population produced a preliminary estimate of DD prevalence in the U.S.” (opens the source at this quote in a new tab)

“As this initial model does not include presymptomatic patients or those presenting with non-HCM phenotypes, such as dilated cardiomyopathy, isolated skeletal myopathy or cognitive impairment, it likely underestimates the true disease burden.” (opens the source at this quote in a new tab)

Estimates from literature, genomic databases, and health records: range of 240 to 11,807, 2026 congress abstract

“DD prevalence estimates were derived based on several approaches: 1) published estimates of DD prevalence in HCM populations were used to estimate a composite prevalence in the overall HCM population, 2) loss-of-function (LoF) LAMP2 variants in genomic databases (gnomAd, AllOfUs, UK Biobank) were used to estimate overall DD prevalence, and 3) the TriNetX EHR database was employed to estimate the number of diagnosed US DD patients, identified with at least 1 instance of ICD10 code E74.05.” (opens the source at this quote in a new tab)

“Estimates based on the published literature considered only DD with HCM phenotype.” (opens the source at this quote in a new tab)

“Differences in the estimates based on the genomic data sources gnomAd, AllOfUs, and the UK Biobank could be explained by recruitment ascertainment, age-distribution, or other factors. In particular, the UK Biobank enrolled persons over 40 years of age, which is beyond the life expectancy of most male DD patients.” (opens the source at this quote in a new tab)

“Application of the 374.05 LAMP2 deficiency ICD10 code (approved in 2024) yielded only 240 EHR-identified DD cases, highlighting the likely profound under-diagnosis of this ultra-rare condition.” (opens the source at this quote in a new tab)

“Using different approaches to calculating the prevalence of DD resulted in an estimated prevalence range of 240 (estimated diagnosed) to 11,807 (population-based genomic testing) patients.” (opens the source at this quote in a new tab)

Company estimate for the United States and Europe, Form 10-K filed February 2026: 15,000 to 30,000

“It is estimated to have a prevalence of 15,000 to 30,000 patients in the U.S. and Europe.” (opens the source at this quote in a new tab)

Company modeled estimate, October 2026: 10,000 to 11,000 in the United States, including about 4,000 males

“Estimated Epidemiology of Danon Disease is 20K+ across US & EU5” (opens the source at this quote in a new tab)

“Independent genotype and phenotype-based analyses converge on similar estimate of 10-11K US patients” (opens the source at this quote in a new tab)

“ESTIMATED DANON POPULATION 10-11K PATIENTS” (opens the source at this quote in a new tab)

“~6-7K Female” (opens the source at this quote in a new tab)

“~4K Male” (opens the source at this quote in a new tab)

“Genetic and clinical analyses converged on a modeled U.S. Danon disease population of approximately 10,000–11,000, including 4,000 males.” (opens the source at this quote in a new tab)

Company modeled estimate, October 2026: stated methods and data sources
ElementQuoted slide text
Genotype-based analysis: basis“Based on comprehensive molecular characterization of confirmed Danon Disease + population genomic anchor”
Genotype-based analysis: anchor“62% (~6.6K)”“Classic loss-of-function LAMP2 variants”“Stop-gain (Nonsense), Frameshift and Canonical splice-site variant categories”
Genotype-based analysis: scaling“38% (~4.1K)”“Other P/LP LAMP2 variants”“includes Start-loss, Exon/gene deletions/duplications, Missense, Synonymous and Intronic variant categories”
Genotype-based analysis: variant records“450+ patient records”“9+ variant categories”“variant records of confirmed DD patients from genetic testing labs Invitae, Ambry Genetics and GeneDx, real-world Natural History Cohorts, Rocket Natural History Study, Repository of published RW Danon patient cases”
Phenotype-based analysis: basis“Based on Danon disease natural history modeling + real-world patient data”
Phenotype-based analysis: anchor“~5.1K”“Age & sex-specific DD yield modeling with HCM population”“HCM & DD claims/EHR databases (Cellworks, Forian) covering >310M lives”
Phenotype-based analysis: scaling“~5.4K”“Pre-cardiomyopathy and DCM Patients”
Phenotype-based analysis: natural history model“Age- and sex-specific natural history model built with 700+ patient data”

“Danon disease prevalence and addressable patient estimates are based on available data and assumptions and are subject to uncertainty. Estimated prevalence and identified patient records do not establish the number of patients eligible for treatment.” (opens the source at this quote in a new tab)

Identified patients in the United States as of July 2026: more than 900

“Over 900 Identified US Danon Disease Patients” (opens the source at this quote in a new tab)

“Representing a current diagnosis rate under 10%” (opens the source at this quote in a new tab)

“Estimated based on Danon true prevalence modeling and patients found” (opens the source at this quote in a new tab)

“Does not include VUS patients; business rules for de-identification and de-duplication” (opens the source at this quote in a new tab)

“Non-sponsored de-identified test data purchased through commercial genetic testing labs” (opens the source at this quote in a new tab)

InstitutionsShare of identified patients
Top 25“30%”
Top 100“60%”
“All Institutions (n=290)”“100%”
Sponsored testing program page: approximately 15,000 in the United States, cited to company data on file

“Approximately 15,000 patients in the United States are living with Danon Disease” (opens the source at this quote in a new tab)

“Rocket Pharmaceuticals. Data on file. Danon Disease.” (opens the source at this quote in a new tab)

Japan: nationwide survey and later count of families

“To clarify the clinicopathological features and management, we performed the first nationwide, questionnaire-based survey on Danon disease in Japan. A total of 39 patients (17 males, 22 females) from 20 families were identified in the analysis.” (opens the source at this quote in a new tab)

“Eighteen of these patients (7 males, 11 females) from 12 families were still alive at the time of the survey.” (opens the source at this quote in a new tab)

“In conclusion, Danon disease is an extremely rare muscular disorder in Japan.” (opens the source at this quote in a new tab)

“With the addition of six newly identified families reported after the survey, we have found 26 families in Japan.” (opens the source at this quote in a new tab)

Diagnosed counts in registries

“Data were from the International Danon Disease Registry and includes retrospective data on 116 patients who provided informed consent between 2005 and 2022.” (opens the source at this quote in a new tab)

“Clinical and genetic data were collected in 16 cardiology centers from 8 European countries.” (opens the source at this quote in a new tab)

“The cohort comprised 30 male and 27 female patients.” (opens the source at this quote in a new tab)

“We analyzed the clinical records of patients with DD from 10 Spanish hospitals.” (opens the source at this quote in a new tab)

“Twenty-seven patients were included (mean age, 31 ± 19 years; 78% women).” (opens the source at this quote in a new tab)

Sex distribution among diagnosed cases

“56 females and 90 males were identified.” (opens the source at this quote in a new tab)

“The analysis included 116 patients with DD (of which 20% [n=23] were international) and was stratified by sex: female (n=64, 55%) and male (n=52, 45%)” (opens the source at this quote in a new tab)

“The features of 20 affected men and 18 affected women in 13 families with genetically confirmed Danon disease were reviewed.” (opens the source at this quote in a new tab)

Sex distribution among identified patients in the United States, company data as of July 2026
SexShare of identified patients
Male“45%”
Female“55%”
Geographic and ancestry distribution

“Data were from the International Danon Disease Registry that includes patients from the United States and Europe who gave consent to be part of the study between 2005 and 2022.” (opens the source at this quote in a new tab)

“The majority of patients in the registry were White (72.4%).” (opens the source at this quote in a new tab)

“The prevalence of DD remains unclear, but it is recognized to affect individuals across various countries and ethnicities” (opens the source at this quote in a new tab)

“The location of the patients was broadly distributed from the north to south in Japan” (opens the source at this quote in a new tab)