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Skeletal muscle pathology of mannosidosis in two siblings with spastic paraplegia
Abstract:
Deficiency of alpha-D-mannosidase was found in two siblings with muscle weakness and spastic paraplegia. A biopsy of the vastus lateralis muscle was studied by light and electron microscopy. Cryostat sections showed mild fiber size variation but no necrosis. Semithin Epon sections revealed many vacuoles in the muscle cells and fibroblasts. Electron microscopy showed that the vacuoles, presumably lysosomal, had a single limiting membrane and contained finely granular or granulo-reticular material, membranous structures, and electron-dense ovoids. The vacuoles were identical with those in lymphocytes and other cells of patients with mannosidosis. Disorganization of sarcomere alignment and widening of intermyofibrillar spaces were also observed. Deficiency of alpha-D-mannosidase is considered to cause slowly progressing degeneration of muscle fibers.
Insights
Alpha-D-mannosidase deficiency causes mannosidosis, leading to muscle weakness and spastic paraplegia. Muscle cell vacuoles observed in siblings suggest progressive muscle fiber degeneration.
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- Mannosidosis is a rare lysosomal storage disorder.
- It results from a deficiency in the enzyme alpha-D-mannosidase.
- This deficiency leads to the accumulation of mannose-rich oligosaccharides in various tissues.
Observation:
- Two siblings presented with muscle weakness and spastic paraplegia.
- Muscle biopsy revealed vacuoles in muscle cells and fibroblasts.
- Electron microscopy confirmed these vacuoles were lysosomal and contained granular material and membranous structures.
Findings:
- The observed vacuoles were consistent with those found in other tissues of mannosidosis patients.
- Muscle fibers showed disorganization of sarcomeres and widened intermyofibrillar spaces.
- Alpha-D-mannosidase deficiency was confirmed as the underlying cause.
Implications:
- This study highlights the impact of alpha-D-mannosidase deficiency on muscle tissue.
- It suggests a mechanism for slowly progressing muscle fiber degeneration in mannosidosis.
- Further research into therapeutic strategies for lysosomal storage disorders affecting muscle is warranted.