RARE DISEASE
Danon disease
Danon disease
Danon disease
Synonyms: GSD due to LAMP-2 deficiency, GSD, type 2B, GSD, type IIb, Glycogen storage disease due to LAMP-2 deficiency, Glycogen storage disease, type 2B, Glycogen storage disease, type IIb, Glycogenosis due to LAMP-2 deficiency, Lysosomal glycogen storage disease with normal acid maltase activity
Synonyms: GSD due to LAMP-2 deficiency, GSD, type 2B, GSD, type IIb, Glycogen storage disease due to LAMP-2 deficiency, Glycogen storage disease, type 2B, Glycogen storage disease, type IIb, Glycogenosis due to LAMP-2 deficiency, Lysosomal glycogen storage disease with normal acid maltase activity
Synonyms: GSD due to LAMP-2 deficiency, GSD, type 2B, GSD, type IIb, Glycogen storage disease due to LAMP-2 deficiency, Glycogen storage disease, type 2B, Glycogen storage disease, type IIb, Glycogenosis due to LAMP-2 deficiency, Lysosomal glycogen storage disease with normal acid maltase activity
Drug discovery
4
drugs
With orphan designations
Overview
Danon Disease Overview
Danon disease is a rare X-linked dominant disorder caused by LAMP2 gene mutations, leading to lysosomal dysfunction and impaired autophagy [1][5][9]. It primarily manifests as cardiomyopathy (hypertrophic or dilated), skeletal myopathy, and intellectual disability, with males exhibiting earlier and more severe symptoms (onset in childhood/adolescence) than females (onset in adulthood) [1][6][17]. Cardiac complications, including heart failure and arrhythmias, are the leading cause of mortality [6][10].
Categories: rare cardiac diseases, rare genetic diseases, rare inborn errors of metabolism, rare neurological diseases, rare transplant-related disorders
Research Papers
87 drug discovery papers related to Danon disease, with 3 first-in-class and 4 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
87 drug discovery papers related to Danon disease, with 3 first-in-class and 4 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-01-21 | Danon disease: Two case reports and literature review.
Danon disease (DD) is an X-linked lysosomal storage disorder caused by LAMP2 variants, with males presenting more severe phenotypes. However, evidence for genotype-phenotype correlation remains limited. This study reports 2 male DD patients with distinct LAMP2 mutations to clarify mutation-specific prognostic differences. A 15-year-old male: chest tightness and palpitations, creatine kinase (CK) 3867 U/L, and hypertrophic cardiomyopathy. A 12-year-old male: exertional dyspnea and syncope, left ventricular ejection fraction 36%, left ventricular thrombus, and CK 5210 U/L. Both were diagnosed with DD via genetic testing: the 15-year-old had a LAMP2 IVS6 + 1G > T splice mutation, and the 12-year-old carried a LAMP2 exon 1 deletion. The 15-year-old underwent heart transplantation followed by immunosuppressive therapy. The 12-year-old received only symptomatic treatment without transplantation. The 15-year-old had normal cardiac function and normalized CK levels during 24-month posttransplant follow-up. The 12-year-old died of heart failure 8 months after diagnosis. LAMP2 mutation types correlate with DD severity. Heart transplantation improves prognosis in severe cases, emphasizing the importance of early diagnosis and intervention.
2026-01-12 | A Rare Cause of Cardiac Hypertrophy: Danon Disease
Cardiac hypertrophy is a common clinical finding and may appear as a cardiac manifestation of numerous diseases. In addition to frequently encountered causes such as hypertension and valvular heart disease, clinicians must also consider cardiac amyloidosis, hypertrophic cardiomyopathies, and various rare genetic conditions. Danon disease is a rare X-linked dominant multisystem disorder characterized by cardiomyopathy, skeletal myopathy, and intellectual disability. It results from defects in the lysosome-associated membrane protein-2 (LAMP2) gene, and numerous pathogenic mutations have been described. Here, we present the case of a 64-year-old woman who was evaluated for suspected cardiac amyloidosis due to marked left ventricular hypertrophy and was subsequently diagnosed with Danon disease. The coexistence of Danon disease and cardiac amyloidosis is exceedingly uncommon and highlights the importance of considering rare etiologies in patients presenting with hypertrophic phenotypes.
2026-01-01 | Fundus imaging in Danon’s disease
A 70-year-old female with Danon’s disease (LAMP2 heterozygous pathogenic variant c.467T>G), status post-cardiac transplantation, presented with 4 years of progressive peripheral visual field disturbances, photophobia, and prolonged dark adaptation. Visual acuity was 20/30 OD and 20/40 OS. Examination revealed pseudophakia OU, and diffuse retinal pigmentary changes [Fig. 1a and 1b]. Widefield fundus autofluorescence (FAF) imaging demonstrated slightly asymmetric diffuse irregularity of the FAF signal [Fig. 1a and b]. Macular optical coherence tomography (OCT) showed outer band irregularities, nodular retinal pigment epithelium (RPE) thickening, and thin choroid [Fig. 1c and d]. Electroretinography (ERG) demonstrated a moderate cone-rod pattern of generalized photoreceptor dysfunction, worse in the left eye [Fig. 2a-d], and superior visual field constriction OU [Fig. 2e and 2f].Figure 1: Multimodal retinal imaging from a 70/F with Danon’s disease showing retinal pigmentary changes and widespread fundus autofluorescence abnormalities (a and b) on ultra-wide field imaging (inset). Optical coherence tomography (OCT) shows outer band irregularities, nodular retinal pigment epithelium thickening (orange arrow), and choroidal thinning (c and d)Figure 2: Light-adapted single flash electroretinogram (ERG) from the right eye (a) and left eye (b) shows a severe reduction in response amplitude. Dark-adapted ERG from the right (c) and left (d) eyes similarly demonstrates subnormal response amplitudes, consistent with global cone- and rod-system dysfunction. Left eye responses were affected more than those of the right eye. Semiautomated kinetic perimetry (e and f) reveals superior constriction and more severe disease in the left eye (e), compared to the right eye (f)Discussion Danon’s disease (OMIM #300257) was first described by Danon et al. in 1981 as a cardiomyopathy caused by structural dysfunction in a lysosomal protein.[1] Additional systemic findings include skeletal myopathy and intellectual disability.[2] Ophthalmic manifestations, reported sparsely, were described much later after the discovery of the disease. Findings include a pigmentary retinopathy, lens changes, ERG abnormalities with cone and rod dysfunction, and visual field changes. Due to X-linked inheritance, males experience more severe disease, often requiring cardiac transplantation by early adulthood, and a limited lifespan.[3] Our patient exhibited extensive peripheral involvement, likely attributable to her age. Her FAF pattern showed mixed hyper- and hypo-autofluorescence, similar to patterns seen in carriers of other X-linked disorders like retinitis pigmentosa and choroideremia.[4] The asymmetry may reflect variable X-chromosome inactivation. Notably, ocular signs may precede serious cardiac disease, underscoring the importance of early eye and genetic evaluation.[5] Authors contributions Sakshi Shiromani: concept, design, literature search, data acquisition, manuscript preparation. Anika Quillin: literature search, data acquisition, manuscript editing, and review. Nieraj Jain: concept, design, data acquisition, definition of intellectual content, manuscript editing, and review Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship: Foundation Fighting Blindness Career Development Award CD-C-0918-0748-EEC (NJ); Research to Prevent Blindness Challenge Grant; National Eye Institute P30EY00630; Sitaraman Family. Conflicts of interest: There are no conflicts of interest.
2026-01-21 | Danon disease: Two case reports and literature review.
Danon disease (DD) is an X-linked lysosomal storage disorder caused by LAMP2 variants, with males presenting more severe phenotypes. However, evidence for genotype-phenotype correlation remains limited. This study reports 2 male DD patients with distinct LAMP2 mutations to clarify mutation-specific prognostic differences. A 15-year-old male: chest tightness and palpitations, creatine kinase (CK) 3867 U/L, and hypertrophic cardiomyopathy. A 12-year-old male: exertional dyspnea and syncope, left ventricular ejection fraction 36%, left ventricular thrombus, and CK 5210 U/L. Both were diagnosed with DD via genetic testing: the 15-year-old had a LAMP2 IVS6 + 1G > T splice mutation, and the 12-year-old carried a LAMP2 exon 1 deletion. The 15-year-old underwent heart transplantation followed by immunosuppressive therapy. The 12-year-old received only symptomatic treatment without transplantation. The 15-year-old had normal cardiac function and normalized CK levels during 24-month posttransplant follow-up. The 12-year-old died of heart failure 8 months after diagnosis. LAMP2 mutation types correlate with DD severity. Heart transplantation improves prognosis in severe cases, emphasizing the importance of early diagnosis and intervention.
2026-01-12 | A Rare Cause of Cardiac Hypertrophy: Danon Disease
Cardiac hypertrophy is a common clinical finding and may appear as a cardiac manifestation of numerous diseases. In addition to frequently encountered causes such as hypertension and valvular heart disease, clinicians must also consider cardiac amyloidosis, hypertrophic cardiomyopathies, and various rare genetic conditions. Danon disease is a rare X-linked dominant multisystem disorder characterized by cardiomyopathy, skeletal myopathy, and intellectual disability. It results from defects in the lysosome-associated membrane protein-2 (LAMP2) gene, and numerous pathogenic mutations have been described. Here, we present the case of a 64-year-old woman who was evaluated for suspected cardiac amyloidosis due to marked left ventricular hypertrophy and was subsequently diagnosed with Danon disease. The coexistence of Danon disease and cardiac amyloidosis is exceedingly uncommon and highlights the importance of considering rare etiologies in patients presenting with hypertrophic phenotypes.
2026-01-01 | Fundus imaging in Danon’s disease
A 70-year-old female with Danon’s disease (LAMP2 heterozygous pathogenic variant c.467T>G), status post-cardiac transplantation, presented with 4 years of progressive peripheral visual field disturbances, photophobia, and prolonged dark adaptation. Visual acuity was 20/30 OD and 20/40 OS. Examination revealed pseudophakia OU, and diffuse retinal pigmentary changes [Fig. 1a and 1b]. Widefield fundus autofluorescence (FAF) imaging demonstrated slightly asymmetric diffuse irregularity of the FAF signal [Fig. 1a and b]. Macular optical coherence tomography (OCT) showed outer band irregularities, nodular retinal pigment epithelium (RPE) thickening, and thin choroid [Fig. 1c and d]. Electroretinography (ERG) demonstrated a moderate cone-rod pattern of generalized photoreceptor dysfunction, worse in the left eye [Fig. 2a-d], and superior visual field constriction OU [Fig. 2e and 2f].Figure 1: Multimodal retinal imaging from a 70/F with Danon’s disease showing retinal pigmentary changes and widespread fundus autofluorescence abnormalities (a and b) on ultra-wide field imaging (inset). Optical coherence tomography (OCT) shows outer band irregularities, nodular retinal pigment epithelium thickening (orange arrow), and choroidal thinning (c and d)Figure 2: Light-adapted single flash electroretinogram (ERG) from the right eye (a) and left eye (b) shows a severe reduction in response amplitude. Dark-adapted ERG from the right (c) and left (d) eyes similarly demonstrates subnormal response amplitudes, consistent with global cone- and rod-system dysfunction. Left eye responses were affected more than those of the right eye. Semiautomated kinetic perimetry (e and f) reveals superior constriction and more severe disease in the left eye (e), compared to the right eye (f)Discussion Danon’s disease (OMIM #300257) was first described by Danon et al. in 1981 as a cardiomyopathy caused by structural dysfunction in a lysosomal protein.[1] Additional systemic findings include skeletal myopathy and intellectual disability.[2] Ophthalmic manifestations, reported sparsely, were described much later after the discovery of the disease. Findings include a pigmentary retinopathy, lens changes, ERG abnormalities with cone and rod dysfunction, and visual field changes. Due to X-linked inheritance, males experience more severe disease, often requiring cardiac transplantation by early adulthood, and a limited lifespan.[3] Our patient exhibited extensive peripheral involvement, likely attributable to her age. Her FAF pattern showed mixed hyper- and hypo-autofluorescence, similar to patterns seen in carriers of other X-linked disorders like retinitis pigmentosa and choroideremia.[4] The asymmetry may reflect variable X-chromosome inactivation. Notably, ocular signs may precede serious cardiac disease, underscoring the importance of early eye and genetic evaluation.[5] Authors contributions Sakshi Shiromani: concept, design, literature search, data acquisition, manuscript preparation. Anika Quillin: literature search, data acquisition, manuscript editing, and review. Nieraj Jain: concept, design, data acquisition, definition of intellectual content, manuscript editing, and review Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship: Foundation Fighting Blindness Career Development Award CD-C-0918-0748-EEC (NJ); Research to Prevent Blindness Challenge Grant; National Eye Institute P30EY00630; Sitaraman Family. Conflicts of interest: There are no conflicts of interest.
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Drug Discovery Landscape
4 orphan drug designations for Danon disease.
4 orphan drug designations for Danon disease.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Adeno-associated viral vector serotype 2i8 containing the human LAMP2 isoform B transgene | gene therapies | EMA | 2025-05-22 | — | AskBio France |
autologous human CD34+ hematopoietic stem and progenitor cells (HSPCs), derived from G-CSF/plerixafor mobilized peripheral blood stem cells (PBSCs) of patients with Danon disease (DD) | cell therapies | FDA | 2024-04-23 | — | Papillon Therapeutics |
Adeno-associated virus serotype 9 vector containing the human LAMP2 isoform B transgene | gene therapies | EMA | 2023-08-16 | — | Rocket Pharmaceuticals B.V. |
Adeno-associated virus serotype 9 vector containing the human lysosome-associated membrane glycoprotein 2 isoform B transgene (AAV9.LAMP2B) | gene therapies | FDA | 2019-02-01 | — | Rocket Pharmaceuticals, Inc. |
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