title: Danon disease with typical early-onset cardiomyopathy in a male: focus on a novel LAMP-2 mutation.
abstract: We report a case of a 16-yr-old male with Danon disease caused by a novel mutation in the LAMP-2 gene. Mutations in the LAMP-2 gene result in the absence of LAMP-2 on immunohistochemical staining of muscle tissue, thus defining Danon disease, a rare X-linked myopathy. It is characterized clinically by HCM or left ventricular hypertrophy, a WPW pattern on ECG, variable degrees of muscular weakness (skeletal myopathy), mental retardation, and retinal changes. The patient presented with severe skeletal muscular weakness and respiratory failure. He also had a history of two OHTs, the first one for severe HCM and the second for allograft rejection. The patient's myopathy was initially presumed to be exclusively related to steroid-induced "critical care myopathy." However, further evaluation with a thigh muscle biopsy revealed autophagic vacuoles with sarcolemnal features suggestive of a lysosomal storage disorder. DNA analysis ultimately identified a previously unreported hemizygous IVS6+3_+6delGAGT splice site deletion mutation in the LAMP-2 gene located within the 5' splice site of intron 6, consistent with Danon disease.
authors.affiliation: Department of Pediatrics, Moffitt Children's Hospital, UCSF, San Francisco, CA 94143, USA. BuiY@peds.ucsf.edu
authors.forename: Yen K
authors.initials: YK
authors.lastname: Bui
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Renella
authors.forename: Julian A
authors.initials: JA
authors.lastname: Martinez-Agosto
authors.forename: Anthony
authors.initials: A
authors.lastname: Verity
authors.forename: Andranik
authors.initials: A
authors.lastname: Madikians
authors.forename: Juan C
authors.initials: JC
authors.lastname: Alejos
mesh_terms: D000293:Adolescent; D009202:Cardiomyopathies / Q000209:etiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D052120:Glycogen Storage Disease Type IIb / Q000150:complications / Q000235:genetics*; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation
chemical_list: C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins