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Infantile autophagic vacuolar myopathy is distinct from Danon disease
A Yamamoto1, Y Morisawa, A Verloes
1Department of Ultrastructural Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo, Japan.
Insights
Danon disease, a lysosomal glycogen storage disorder, results from LAMP-2 deficiency. Infantile cases with similar features but present LAMP-2 protein are distinct and may resemble X-linked myopathy with excessive autophagy.
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- Danon disease is a rare genetic disorder caused by mutations in the lysosome-associated membrane protein-2 (LAMP-2) gene, leading to lysosomal dysfunction and glycogen accumulation.
- It typically manifests in adolescence or adulthood, characterized by cardiomyopathy, intellectual disability, and skeletal myopathy.
Observation:
- Two infantile patients presented with clinical and histological features mimicking Danon disease.
- However, unlike classic Danon disease, LAMP-2 protein was present in the skeletal muscle of these infants.
- One patient showed C5b-9 deposition and multilayered basal lamina, suggesting a different underlying pathology.
Findings:
- The infantile disorder, despite overlapping features, is distinct from Danon disease due to the presence of LAMP-2 protein.
- The observed pathological features in one infant suggest a potential link to X-linked myopathy with excessive autophagy.
Implications:
- This distinction is crucial for accurate diagnosis and understanding the pathogenesis of infantile lysosomal storage disorders.
- Further research is needed to elucidate the specific genetic and molecular mechanisms underlying this infantile myopathy.
- Identifying distinct disease entities aids in developing targeted therapeutic strategies for glycogen storage diseases.
Abstract:
Lysosomal glycogen storage disease with normal acid maltase (Danon) is caused by primary lysosome-associated membrane protein-2 (LAMP-2) deficiency. Typically, the disease begins after the first decade; however, two infantile patients had similar histologic features. The infantile disorder is distinct from Danon disease, because, in both infants, LAMP-2 protein is present in skeletal muscle. Deposition of C5b-9 and multilayered basal lamina in one patient suggest that the infantile disease is pathogenically similar to X-linked myopathy with excessive autophagy.