Skeletal muscle pathology of mannosidosis in two siblings with spastic paraplegia.

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.