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Danon disease with typical early‐onset cardiomyopathy in a male: Focus on a novel LAMP‐2 mutation
Author(s) -
Bui Yen K.,
Renella Pierangelo,
MartinezAgosto Julian A.,
Verity Anthony,
Madikians Andranik,
Alejos Juan C.
Publication year - 2008
Publication title -
pediatric transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.457
H-Index - 69
eISSN - 1399-3046
pISSN - 1397-3142
DOI - 10.1111/j.1399-3046.2007.00874.x
Subject(s) - myopathy , medicine , cardiomyopathy , muscle biopsy , pathology , mutation , splice site mutation , muscular dystrophy , gene mutation , hypertrophic cardiomyopathy , exon , heart failure , biopsy , genetics , gene , biology , alternative splicing
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.