Danon disease presenting with dilated cardiomyopathy and a complex phenotype.
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.
Taylor
Matthew R G
MRG
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.
Ku
Lisa
L
University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
Slavov
Dobromir
D
University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
Cavanaugh
Jean
J
The Children's Hospital, Denver, CO, USA.
Boucek
Mark
M
The Children's Hospital, Denver, CO, USA.
Zhu
Xiao
X
University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
Graw
Sharon
S
University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
Carniel
Elisa
E
University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
Barnes
Carl
C
University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
Quan
Dianna
D
University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
Prall
Ryan
R
University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
Lovell
Mark A
MA
The Children's Hospital, Denver, CO, USA.
Mierau
Gary
G
The Children's Hospital, Denver, CO, USA.
Ruegg
Patsy
P
University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
Mandava
Naresh
N
University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
Bristow
Michael R
MR
University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
Towbin
Jeffrey A
JA
Baylor College of Medicine, Houston, TX, USA.
Mestroni
Luisa
L
University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
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
C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins