BACKGROUND: Danon disease is an X-linked dominant disorder; concentric left ventricular hypertrophy (LVH) is one of its manifestations. In this study, we investigated the prevalence of Danon disease in patients with concentric LVH who underwent endomyocardial biopsy (EMB). METHODS AND RESULTS: A total of 50 patients with concentric LVH underwent EMB from January 2008 to December 2010. Cardiac amyloidosis was diagnosed in 14 patients; genetic analysis of lysosome-associated membrane protein 2 (LAMP2) was done in the remaining 36 patients. Three novel LAMP2 frameshift mutations were found. They were c.808_809 insG in exon 6, c.320_321 insCATC in exon 3, and c.257_258delCC in exon 3, leading to a premature stop codon on cDNA analysis. The prevalence of Danon disease was seen in 6% (3 of 50) of unselected concentric LVH patients who underwent EMB, or 8% (3 of 36) after excluding cardiac amyloidosis through EMB. All the three patients were male teenagers with a mean age of 15 ± 1 years, and had mild mental retardation, two of the three with Wolff-Parkinson-White (WPW) syndrome and markedly increased left ventricular voltage. All the three patients had increased serum hepatic enzymes and creatine kinase (CK) concentrations. There was no death or cardiovascular hospitalization during 20 ± 15 months of follow-up. CONCLUSIONS: Danon disease may account for a number of patients with concentric LVH who underwent EMB. Danon disease should be suspected in the male teenager with concentric LVH, especially with elevated serum hepatic enzymes and CK concentrations, and/or WPW syndrome with markedly increased voltage of the left ventricle. Genetic analysis of LAMP2 can help make the diagnosis.
BACKGROUND: Danon disease is an X-linked dominant disorder; concentric left ventricular hypertrophy (LVH) is one of its manifestations. In this study, we investigated the prevalence of Danon disease in patients with concentric LVH who underwent endomyocardial biopsy (EMB). METHODS AND RESULTS: A total of 50 patients with concentric LVH underwent EMB from January 2008 to December 2010. Cardiac amyloidosis was diagnosed in 14 patients; genetic analysis of lysosome-associated membrane protein 2 (LAMP2) was done in the remaining 36 patients. Three novel LAMP2 frameshift mutations were found. They were c.808_809 insG in exon 6, c.320_321 insCATC in exon 3, and c.257_258delCC in exon 3, leading to a premature stop codon on cDNA analysis. The prevalence of Danon disease was seen in 6% (3 of 50) of unselected concentric LVH patients who underwent EMB, or 8% (3 of 36) after excluding cardiac amyloidosis through EMB. All the three patients were male teenagers with a mean age of 15 ± 1 years, and had mild mental retardation, two of the three with Wolff-Parkinson-White (WPW) syndrome and markedly increased left ventricular voltage. All the three patients had increased serum hepatic enzymes and creatine kinase (CK) concentrations. There was no death or cardiovascular hospitalization during 20 ± 15 months of follow-up. CONCLUSIONS: Danon disease may account for a number of patients with concentric LVH who underwent EMB. Danon disease should be suspected in the male teenager with concentric LVH, especially with elevated serum hepatic enzymes and CK concentrations, and/or WPW syndrome with markedly increased voltage of the left ventricle. Genetic analysis of LAMP2 can help make the diagnosis.
Authors: Matthew A Lines; Stacy Hewson; William Halliday; Peter J B Sabatini; Tracy Stockley; Anne I Dipchand; Sarah Bowdin; Komudi Siriwardena Journal: JIMD Rep Date: 2013-11-13
Authors: Massimiliano Cecconi; Maria I Parodi; Francesco Formisano; Paolo Spirito; Camillo Autore; Maria B Musumeci; Stefano Favale; Cinzia Forleo; Claudio Rapezzi; Elena Biagini; Sabrina Davì; Elisabetta Canepa; Loredana Pennese; Mauro Castagnetta; Dario Degiorgio; Domenico A Coviello Journal: Int J Mol Med Date: 2016-09-07 Impact factor: 4.101
Authors: P Mueller; C H Attenhofer Jost; M Rohrbach; E R Valsangiacomo Buechel; B Seifert; C Balmer; O Kretschmar; M R Baumgartner; R Weber Journal: Int J Cardiol Heart Vessel Date: 2013-11-13
Authors: Jiri Gurka; Lenka Piherova; Filip Majer; Anna Chaloupka; Daniela Zakova; Ondrej Pelak; Alice Krebsova; Petr Peichl; Jan Krejci; Tomas Freiberger; Vojtech Melenovsky; Josef Kautzner; Tomas Kalina; Jakub Sikora; Milos Kubanek Journal: ESC Heart Fail Date: 2020-07-13