Danon disease is a rare X-linked dominant lysosomal disease due to the primary deficiency of lysosome-associated membrane protein 2 (LAMP2) gene. Cardiomyopathy, skeletal myopathy and mental retardation are the typical triad of Danon disease. More than 60 LAMP2 mutations have been reported. The molecular mechanism is defects in LAMP2 protein (due to LAMP2 mutation) which causes insidious glycogen accumulation in cardiac muscle cells and resulting in cardiac hypertrophy and electrophysiological abnormalities. However, there are significant differences between the male and female Danon disease patients with regard to clinical features and cardiac manifestations. The clinical symptoms are variable, from asymptomatic to sudden cardiac death. Wolff–Parkinson–White syndrome is more common in male than female patients. Hypertrophic cardiomyopathy is predominant in male patients, whereas the similar prevalence of hypertrophic and dilated cardiomyopathy in female patients. Male patients are diagnosed usually at teenage, whereas the diagnosis and events occurred approximately 15 years later in female than male patients. Heart transplantation is the reliable treatment once the occurrence of heart failure and should be considered as early as possible due to its rapid progression.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $37.50 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Danon, M.J., Oh, S.J., DiMauro, S., Manaligod, J.R., Eastwood, A., Naidu, S. et al. Lysosomal glycogen storage disease with normal acid maltase. Neurology 31, 51–57 (1981).
Nishino, I., Fu, J., Tanji, K., Yamada, T., Shimojo, S., Koori, T. et al. Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease). Nature 406, 906–910 (2000).
Cheng, Z., Cui, Q., Tian, Z., Xie, H., Chen, L., Fang, L. et al. Danon disease as a cause of concentric left ventricular hypertrophy in patients who underwent endomyocardial biopsy. Eur. Heart J. 33, 649–656 (2012).
Cottinet, S.L., Bergemer-Fouquet, A.M., Toutain, A., Sabourdy, F., Maakaroun-Vermesse, Z., Levade, T. et al. Danon disease: intrafamilial phenotypic variability related to a novel LAMP-2 mutation. J. Inherit. Metab. Dis. 34, 515–522 (2011).
Boucek, D., Jirikowic, J., Taylor, M. Natural history of Danon disease. Genet. Med. 13, 563–568 (2011).
Kim, H., Cho, A., Lim, B.C., Kim, M.J., Kim, K.J., Nishino, I. et al. A 13-year-old girl with proximal weakness and hypertrophic cardiomyopathy with Danon disease. Muscle Nerve 41, 879–882 (2010).
Yang, Z., Funke, B.H., Cripe, L.H., Vick, G.W., Mancini-Dinardo, D., Peña, L.S. et al. LAMP2 microdeletions in patients with Danon disease. Circ.Cardiovasc. Genet. 3, 129–137 (2010).
Toib, A., Grange, D.K., Kozel, B.A., Ewald, G.A., White, F.V., Canter, C.E. Distinct clinical and histopathological presentations of Danon cardiomyopathy in young women. J. Am. Coll. Cardiol. 55, 408–410 (2010).
Sabourdy, F., Michelakakis, H., Anastasakis, A., Garcia, V., Mavridou, I., Nieto, M. et al. Danon disease: further clinical and molecular heterogeneity. Muscle Nerve 39, 837–844 (2009).
Regelsberger, G., Höftberger, R., Pickl, W.F., Zlabinger, G.J., Körmöczi, U., Salzer-Muhar, U. et al. Danon disease: case report and detection of new mutation. J. Inherit. Metab. Dis. doi:10.1007/s10545-009-1097-9. (2009).
Dougu, N., Joho, S., Shan, L., Shida, T., Matsuki, A., Uese, K. et al. Novel LAMP-2 mutation in a family with Danon disease presenting with hypertrophic cardiomyopathy. Circ. J. 73, 376–380 (2009).
Sugie, K., Yamamoto, A., Murayama, K., Oh, S.J., Takahashi, M., Mora, M. et al. Clinicopathological features of genetically confirmed Danon disease. Neurology 58, 1773–1778 (2002).
Mattei, M.G., Matterson, J., Chen, J.W., Williams, M.A., Fukuda, M. Two human lysosomal membrane glycoproteins, h-lamp-1 and h-lamp-2, are encoded by genes localized to chromosome 13q34 and chromosome Xq24-25, respectively. J. Biol. Chem. 265, 7548–7551 (1990).
Maron, B.J., Roberts, W.C., Arad, M., Haas, T.S., Spirito, P., Wright, G.B. et al. Clinical outcome and phenotypic expression in LAMP2 cardiomyopathy. JAMA 301, 1253–1259 (2009).
Arad, M., Maron, B.J., Gorham, J.M., Johnson, W.H., Saul, J.P., Perez-Atayde, A.R. et al. Glycogen storage diseases presenting as hypertrophic cardiomyopathy. N. Engl. J. Med. 352, 362–372 (2005).
Miani, D., Taylor, M., Mestroni, L., D'Aurizio, F., Finato, N., Fanin, M. et al. Sudden death associated with danon disease in women. Am. J. Cardiol. 109, 406–411 (2012).
Di Blasi, C., Jarre, L., Blasevich, F., Dassi, P., Mora, M. Danon disease: a novel LAMP2 mutation affecting the pre-mRNA splicing and causing aberrant transcripts and partial protein expression. Neuromuscul. Disord. 18, 962–966 (2008).
Iascone, M., Iacovoni, A., Marchetti, D., Ferrazzi, P. Gene symbol: LAMP2. Disease: Danon disease. Hum. Genet. 123, 537 (2008).
van der Kooi, A.J., van Langen, I.M., Aronica, E., van Doorn, P.A., Wokke, J.H., Brusse, E. et al. Extension of the clinical spectrum of Danon disease. Neurology 70, 1358–1359 (2008).
Bui, Y.K., Renella, P., Martinez-Agosto, J.A., Verity, A., Madikians, A., Alejos, J.C. Danon disease with typical early-onset cardiomyopathy in a male: focus on a novel LAMP-2 mutation. Pediatr. Transplant 12, 246–250 (2008).
Nadeau, A., Therrien, C., Karpati, G., Sinnreich, M. Danon disease due to a novel splice mutation in the LAMP2 gene. Muscle Nerve 37, 338–342 (2008).
Tuñón, T., Guerrero, D., Urchaga, A., Nishino, I., Ayuso, T., Matsuda, Y. et al. Danon disease: a novel Lamp-2 gene mutation in a family with four affected members. Neuromuscul. Disord. 18, 167–174 (2008).
Taylor, M.R., Ku, L., Slavov, D., Cavanaugh, J., Boucek, M., Zhu, X. et al. Danon disease presenting with dilated cardiomyopathy and a complex phenotype. J. Hum. Genet. 52, 830–835 (2007).
Fanin, M., Nascimbeni, A.C., Fulizio, L., Spinazzi, M., Melacini, P., Angelini, C. Generalized lysosome-associated membrane protein-2 defect explains multisystem clinical involvement and allows leukocyte diagnostic screening in Danon disease. Am. J. Pathol. 168, 1309–1320 (2006).
Echaniz-Laguna, A., Mohr, M., Epailly, E., Nishino, I., Charron, P., Richard, P. et al. Novel Lamp-2 gene mutation and successful treatment with heart transplantation in a large family with Danon disease. Muscle Nerve 33, 393–397 (2006).
Yang, Z., McMahon, C.J., Smith, L.R., Bersola, J., Adesina, A.M., Breinholt, J.P. et al. Danon disease as an underrecognized cause of hypertrophic cardiomyopathy in children. Circulation 112, 1612–1617 (2005).
Balmer, C., Ballhausen, D., Bosshard, N.U., Steinmann, B., Boltshauser, E., Bauersfeld, U. et al. Familial X-linked cardiomyopathy (Danon disease): diagnostic confirmation by mutation analysis of the LAMP2gene. Eur. J. Pediatr. 164, 509–514 (2005).
Lobrinus, J.A., Schorderet, D.F., Payot, M., Jeanrenaud, X., Bottani, A., Superti-Furga, A. et al. Morphological, clinical and genetic aspects in a family with a novel LAMP-2 gene mutation (Danon disease). Neuromuscul. Disord. 15, 293–298 (2005).
Musumeci, O., Rodolico, C., Nishino, I., Di Guardo, G., Migliorato, A., Aguennouz, M. et al. Asymptomatic hyperCKemia in a case of Danon disease due to a missense mutation in Lamp-2 gene. Neuromuscul. Disord. 15, 409–411 (2005).
Charron, P., Villard, E., Sébillon, P., Laforêt, P., Maisonobe, T., Duboscq-Bidot, L. et al. Danon's disease as a cause of hypertrophic cardiomyopathy: a systematic survey. Heart 90, 842–846 (2004).
Horváth, J., Ketelsen, U.P., Geibel-Zehender, A., Boehm, N., Olbrich, H., Korinthenberg, R. et al. Identification of a novel LAMP2 mutation responsible for X-chromosomal dominant Danon disease. Neuropediatrics 34, 270–273 (2003).
Lacoste-Collin, L., Garcia, V., Uro-Coste, E., Arné-Bes, M.C., Durand, D., Levade, T. et al. Danon's disease (X-linked vacuolar cardiomyopathy and myopathy): a case with a novel Lamp-2 gene mutation. Neuromuscul. Disord. 12, 882–885 (2002).
Takahashi, M., Yamamoto, A., Takano, K., Sudo, A., Wada, T., Goto, Y. et al. Germline mosaicism of a novel mutation in lysosome-associated membrane protein-2 deficiency (Danon disease). Ann. Neurol. 52, 122–125 (2002).
About this article
Multidisciplinary Cardiovascular Annals (2019)
Genetics and Molecular Biology (2019)
Developmental Neurorehabilitation (2019)
How to diagnose heart failure with preserved ejection fraction: the HFA–PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)
European Heart Journal (2019)
A new phenotype of severe dilated cardiomyopathy associated with a mutation in the LAMP2 gene previously known to cause hypertrophic cardiomyopathy in the context of Danon disease
European Journal of Medical Genetics (2019)