title: Danon disease presenting with dilated cardiomyopathy and a complex phenotype.
abstract: X-linked dilated cardiomyopathy (XLCM) was first described in 1987 and associated with dystrophin gene (DMD) mutations a decade later in one of the original two families. Here we report long-term follow-up of the second family (XLCM-2), for which a DMD mutation was never found. Analysis of the lysosome-associated membrane protein-2 (LAMP-2) gene detected a novel mutation, confirming a diagnosis of Danon disease. The broad phenotype in this family included dilated and hypertrophic cardiomyopathy, cardiac pre-excitation, skeletal myopathy with high serum creatinine kinase, cognitive impairement (in males), and and a pigmentary retinopathy in affected females. Cardiac biopsy in a 13-month-old mutation-carrying male showed no vacuolization by standard histology. We conclude that XLCM may be the presenting sign of Danon disease and, in the presence of familial history of HCM, pre-excitation, skeletal muscle involvement and retinal pigmentary dystrophy should prompt LAMP-2 clinical testing. Furthermore, the absence of vacuolar myopathy in biopsies from young patients may not exclude Danon disease.
authors: University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA. matthew.taylor@uchsc.edu.|, 12635 East Montview Blvd. Suite 100, Aurora, CO, 80045, USA. matthew.taylor@uchsc.edu.
authors: Matthew R G
authors: MRG
authors: Taylor
authors: University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
authors: Lisa
authors: L
authors: Ku
authors: University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
authors: Dobromir
authors: D
authors: Slavov
authors: The Children's Hospital, Denver, CO, USA.
authors: Jean
authors: J
authors: Cavanaugh
authors: The Children's Hospital, Denver, CO, USA.
authors: Mark
authors: M
authors: Boucek
authors: University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
authors: Xiao
authors: X
authors: Zhu
authors: University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
authors: Sharon
authors: S
authors: Graw
authors: University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
authors: Elisa
authors: E
authors: Carniel
authors: University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
authors: Carl
authors: C
authors: Barnes
authors: University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
authors: Dianna
authors: D
authors: Quan
authors: University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
authors: Ryan
authors: R
authors: Prall
authors: The Children's Hospital, Denver, CO, USA.
authors: Mark A
authors: MA
authors: Lovell
authors: The Children's Hospital, Denver, CO, USA.
authors: Gary
authors: G
authors: Mierau
authors: University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
authors: Patsy
authors: P
authors: Ruegg
authors: University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
authors: Naresh
authors: N
authors: Mandava
authors: University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
authors: Michael R
authors: MR
authors: Bristow
authors: Baylor College of Medicine, Houston, TX, USA.
authors: Jeffrey A
authors: JA
authors: Towbin
authors: University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
authors: Luisa
authors: L
authors: Mestroni
mesh_terms: D000293:Adolescent; D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D005260:Female; D052120:Glycogen Storage Disease Type IIb / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins