[Morphological and clinical aspects of Danon disease].

Background: Danon disease, an X-linked hypertrophic cardiomyopathy, is caused by primary deficiency of lysosome-associated membrane protein (LAMP-2). The pathological hallmark of the disease is the appearance of intracytoplasmic vacuoles containing autophagic material and the absence of LAMP-2 activity in the muscle.

Aim: To define the LAMP-2 protein deficiency we investigated cardiac and skeletal muscle of a 19-year-old man with hypertrophic cardiomyopathy without clinically apparent skeletal myopathy or mental impairment, whose mother died suddenly at 46 years of age.

Methods: Clinical, morphological, immunohistochemical and ultrastructural analysis was performed. Paraffin sections of cardiac muscle were stained using routine histochemical methods. Frozen sections of skeletal muscle were stained using histochemical methods as well as using monoclonal antisera against N-terminal of dystrophin and antisera against LAMP-2. Ultrastructural examination of both cardiac and skeletal muscle specimens were performed.

Results: Cardiac and skeletal muscle revealed an excessive accumulation of early and late autophagic vacuoles containing various cytoplasmic debris. In immunohistochemical analysis the vacuolar membrane seen in skeletal muscle was decorated with antibody against dystrophin and such vacuoles were negative for LAMP-2.

Conclusion: Ultrastructural and immunohistochemical analysis of skeletal muscle (less invasive than myocardial biopsy) may be used in diagnosis of Danon disease. Early diagnosis of Danon disease is important for timely cardiac transplantation, the only effective therapeutic option.