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Danon Disease

GSD due to LAMP-2 Deficiency


  • In 1 family the proband initially presented with HCM as a teenager, which progressed to dilated cardiomyopathy (DCM) and heart failure. Skeletal myopathy and WPW were also noted.[ncbi.nlm.nih.gov]
  • The rearrangement results in a plethora of abnormal LAMP2 splicing variants and also in use of likely cryptic splice sites in the 3' terminus of LAMP2 gene.[ncbi.nlm.nih.gov]
  • A chest X-ray showed cardiomegaly with massive pulmonary congestion. Transthoracic echocardiography demonstrated biventricular symmetrical concentric hypertrophy without left and right outflow tract gradient.[revespcardiol.org]
  • Autopsy or explant specimens examined at the time of transplantation reveal cardiomegaly with ventricular hypertrophy and biatrial and biventricular dilatation.[flipper.diff.org]
  • Our patients showed the full spectrum of both prenatal signs (hydrops, polyhydramnios) and postnatal signs (hypotonia, hyporeflexia, absence of active movements, cardiomegaly), which have been reported previously.[link.springer.com]
  • It was initially described by Danon MJ in 1981, who described two 16-year-old men with mental retardation, cardiomegaly, and proximal skeletal myopathy, in whom they demonstrated accumulation of glycogen in their muscles without alterations in the enzymes[scielo.org.mx]
  • A pathological study of his heart ( Figure 2A through 2D ) showed marked cardiomegaly (weight, 1266 g) and diffuse hypertrophy. Histopathological examination showed myocyte hypertrophy and prominent interstitial fibrosis.[nejm.org]
Retinal Pigmentation
  • In the eye, LAMP2 is expressed only in the retinal pigment epithelium. This study aimed to investigate the previously unreported impact of LAMP2 mutations on the electrooculogram generated by the retinal pigment epithelium.[ncbi.nlm.nih.gov]
  • Some females may have visual disturbances, and/or retinal pigment abnormalities Danon Disease is rare and unfamiliar to most physicians.[en.wikipedia.org]
  • Males demonstrated a near complete loss of pigment in the retinal pigment epithelium.[iovs.arvojournals.org]
  • 1 A family with Danon disease caused by a splice site mutation in LAMP2 that generates a truncated protein. ( 30714332 ) 2019 2 Retinal dystrophy associated with Danon disease and pathogenic mechanism through LAMP2-mutated retinal pigment epithelium.[malacards.org]
Proximal Muscle Weakness
  • We describe two patients: the first patient presented with severe hypertrophic cardiomyopathy, Wolff-Parkinson-White syndrome, proximal muscle weakness, and chronic painless diarrhea; the second patient manifested as limb-girdle muscle weakness, mild[ncbi.nlm.nih.gov]
  • Myopathy Skeletal myopathy manifests as progressive proximal muscle weakness of the shoulders, neck, and legs 1 in 80% to 90% of men. 16 , 25 Weakness is seldom debilitating, and patients usually retain the ability to walk as adults.[circheartfailure.ahajournals.org]
Diffuse Muscle Wasting
  • On neurological examination, he complained of visual loss, and diffuse muscle wasting and weakness were also unexpectedly noted. Electromyography evidenced a myopathic pattern and a peripheral neuropathy.[ncbi.nlm.nih.gov]
Diffuse Muscle Wasting
  • On neurological examination, he complained of visual loss, and diffuse muscle wasting and weakness were also unexpectedly noted. Electromyography evidenced a myopathic pattern and a peripheral neuropathy.[ncbi.nlm.nih.gov]
Cognitive Disorder
  • It is characterized by the development of cardiac disease, skeletal myopathy and cognitive disorder.[ncbi.nlm.nih.gov]
  • Learning or cognitive disorders were reported in 100% of men and, surprisingly, in approximately 50% of women.[nature.com]
  • This patient with a neglected Danon disease, experienced an unusual complication as a stroke due to cerebral hypoperfusion after cardiac arrest caused by WPW syndrome. Copyright 2016 Elsevier B.V. All rights reserved.[ncbi.nlm.nih.gov]
Limb Weakness
  • RESULTS: Patient A had fluctuating limb weakness during 6 months follow-up and was diagnosed with drug-induced myopathy due to anti-hepatitis B therapy with lamivudine.[ncbi.nlm.nih.gov]


  • Early involvement of electrophysiology and early consideration of ICD implantation for symptomatic arrhythmias Skeletal myopathy Formal neuromuscular evaluation Physical therapy and rehabilitation Muscle biopsy may be performed as part of diagnostic workup[circheartfailure.ahajournals.org]
Prolonged PR Interval
  • One male patient showed initial QRS complex slurring with prolonged PR interval. However, the presence of an accessory pathway was excluded by an EP study in all patients.[ncbi.nlm.nih.gov]


  • Examinations performed before and during treatment included visual acuity (VA), spectral-domain optical coherence tomography, and electroretinography. Following total 48 weeks of treatment, VA decreased from 20/30 OD, 20/200 OS, to 20/40 OD, CF OS.[ncbi.nlm.nih.gov]
  • Treatment: There is no specific treatment for this disorder. Treatment is based specifically on any present symptoms and also aims to provide support in the care of the individual. Most treatment is based on heart problems related to this disorder.[medigoo.com]
  • Eye exam LAMP2 gene testing Treatment There is no approved treatment for Danon disease. Treatment is directed toward the specific symptoms that are apparent in each individual and specific myopathies.[raredr.com]
  • Treatment Treatment Options: No known treatment is available for the ocular disease. Transplantation can be an effective treatment for the cardiomyopathy which can be lethal even in adolescents.[disorders.eyes.arizona.edu]


  • Female patients most often present with late-onset cardiomyopathy and slow disease progression, but early-onset cases with unfavorable prognosis have been reported.[ncbi.nlm.nih.gov]
  • Given the poor prognosis associated with cardiomyopathy due to LAMP2 mutation, early diagnosis is critical for determining the appropriate treatment strategy and achieving timely cardiac transplantation, the only effective therapeutic option.[revespcardiol.org]
  • In this study, we report details of the clinical Danon disease phenotype and prognosis based on data from 82 individuals from 36 families with Danon disease that contacted our group.[nature.com]
  • Prognosis Patients are at risk of sudden death due to arrhythmia during early adulthood. The documents contained in this web site are presented for information purposes only.[orpha.net]
  • […] with Danon disease. ( 29175505 ) Yoshida S....Hayashi K. 2018 7 A Mild Version of Danon Disease Caused by a Newly Recognized Mutation in the Lysosome-associated Membrane Protein-2 Gene. ( 29637036 ) Kyaw H....Shinnar M. 2018 8 Clinical Findings and Prognosis[malacards.org]


  • KEYWORDS: Cardiomyopathy, hypertrophic/diagnosis; defibrillators, implantable; glycogen storage cardiomyopathy; glycogen storage disease type IIb/diagnosis; hypertrophic cardiomyopathy/diagnosis; left ventricular hypertrophy/etiology; lysosomal storage[ncbi.nlm.nih.gov]
  • Etiology The disease is caused by mutations in the LAMP2 gene, localised to Xq24. The LAMP2 protein is an essential component of the lysosomal membrane and appears to play a role in autophagosome-lysosome fusion.[orpha.net]
  • Keywords : Autophagy, neurodegenerative disorders, neurodevelopmental disorders, psychiatric disorders, etiology, treatment mechanism Important Note : All contributions to this Research Topic must be within the scope of the section and journal to which[frontiersin.org]
  • On echocardiography, the characteristic appearance includes a thickened ventricular septum and left ventricular posterior wall without an obvious etiology (eg, hypertension, aortic stenosis).[emedicine.medscape.com]


  • Summary Epidemiology More than 20 families have been described in the literature so far. Clinical description The disease classically manifests in males over 10 years of age.[orpha.net]
  • EPIDEMIOLOGY The incidence of Danon Disease has not been determined. HCM is estimated to be present in 2 of every 1000 young adults, according to one large study. Charron et al. examined 197 independent index cases with HCM.[flipper.diff.org]
  • Conclusions: Danon disease requires further studies in order to obtain epidemiological data for this condition. To date, only mutations in the LAMP2 gene have been documented as the main etiology of Danon disease.[scielo.org.mx]
  • […] to the late-onset cases that can occur, may result from an uneven distribution of LAMP2 protein in cardiac muscle, with the protein lacking in some large portions of the muscle, while its expression is preserved in other large myocardial areas. [7] Epidemiology[emedicine.medscape.com]
  • Epidemiology The prevalence of Danon disease is unknown, and as cases have been described around the world, it can likely affect any ethnic group. 5 The observed prevalence may be rising because of increased detection from wider availability of LAMP2[circheartfailure.ahajournals.org]
Sex distribution
Age distribution


  • However, the precise pathophysiological mechanism through which LAMP-2 deficiency causes Danon disease is still not fully understood and its elucidation would promote the development of new therapies.[ncbi.nlm.nih.gov]
  • These models will be validated by determining their distinct pathophysiologic characteristics in comparison to those from both Danon patients and wild type controls.[grantome.com]
  • Nishino & Hiroyasu Tsukaguchi Scientific Reports (2018) In situ measurement of autophagy under nutrient starvation based on interfacial pH sensing Toshiya Sakata, Akiko Saito & Haruyo Sugimoto Scientific Reports (2018) Targeting autophagy in obesity: from pathophysiology[doi.org]


  • Abstract We report the case of an 18-year-old man with Danon disease, a genetic disorder inclunding a severe hypertrophic cardiomyopathy with very broad QRS, who had an implantable cardioverter defibrillator for primary prevention.[ncbi.nlm.nih.gov]
  • Other affected males have dilated cardiomyopathy, which is a condition that weakens and enlarges the heart, preventing it from pumping blood efficiently. Some affected men with hypertrophic cardiomyopathy later develop dilated cardiomyopathy.[ghr.nlm.nih.gov]
  • This DNA vaccine has the potential to be a safe and effective therapy to prevent Alzheimer disease. He described Machado-Joseph disease (MJD), an autosomal dominant ataxia, with William Nyhan, M.D. Ph.D, in 1976, for the first time.[books.google.com]
  • Conway A, McCarthy AL, Lawrence P, et al The prevention, detection and management of cancer treatment-induced cardiotoxicity: a meta-review. BMC Cancer 2015; 15:366. 14.[journals.lww.com]

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