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- Title
Danon disease (autophagic vacuolar myopathy): clinicopathologic features of a kindred.
- Authors
McComb, Rodney D.; Radio, Stanley J.; McAllister, Janice L.; Erickson, Christopher C.; Pattee, Gary L.; Moore, Steven A.
- Abstract
Danon disease, an X-linked dominant disorder caused by a deficiency of lysosome-associated membrane protein-2 (LAMP-2), typically manifests as hypertrophic cardiomyopathy (HCM), skeletal myopathy, and sudden death in males in the second decade, and dilated cardiomyopathy (DCM) in females in later decades. We present a three-generation kindred, including three half-brothers who developed HCM. Two died suddenly at ages 18 and 13 years. The other, our index case, underwent successful heart transplantation at age 16 years. Their mother developed DCM and mild proximal myopathy in her early thirties. Skeletal muscle biopsy from the index case showed numerous basophilic autophagic vacuoles with esterase activity, dystrophin, and dystrophin-associated glycoproteins. Invagination of the sarcolemma, including extracellular matrix, and internalization of capillaries were also prominent but less frequent. Cardiac muscle contained similar vacuoles. Deficiency of LAMP-2 was confirmed in both cardiac and skeletal muscle, whereas LAMP-1 was expressed normally. Autophagic vacuoles were not encountered in skeletal muscle from the mother. This kindred emphasizes the severity of cardiac involvement in males with Danon disease and the need for early transplantation. Pathologic features are similar in cardiac and skeletal muscle of affected males, and can be minimal in female heterozygotes.
- Subjects
HYPERTROPHIC cardiomyopathy; HEART transplantation; AUTOPHAGY; DYSTROPHIN; SARCOLEMMA; EXTRACELLULAR matrix; MYOCARDIUM
- Publication
FASEB Journal, 2007, Vol 21, Issue 5, pA399
- ISSN
0892-6638
- Publication type
Article