Figure 4
Ultrastructural disease correlates with response to ERT. (a) Myocytes with early Stage 1 or 2 ultrastructural disease predominate in the baseline biopsy of patient A, a good histologic responder. Most cells are full of intact myofibrils with lysosomal glycogen tucked in between (4500 × ). (b) Myocytes with late Stage 3 or 4 ultrastructural disease predominate in the baseline biopsy of patient C, a poor histologic responder. Most cells lack myofibrillar structure and are filled with glycogen lakes and debris ( × 4500). (c) High-power view of the variation in cell damage ( × 6500). The upper cell with early Stage 2 disease consists of many intact contractile elements with fraying at the fibril ends and peripheral, membrane-bound glycogen (broken arrow). The lower cell with Stage 4 disease has been completely replaced by cytoplasmic glycogen (solid arrow). Ruptured lysosomal membranes float freely in the lake of glycogen. No contractile elements or mitochondria remain. (d) High-power view of a cell with early Stage 2 disease demonstrates abnormally shaped mitochondria and cytoplasmic glycogen beginning to accumulate between contractile elements ( × 8500). (e) Satellite cells (red arrow) can be seen, by electron microscopy, beneath the basement membrane adjacent to damaged myocytes (black asterix; EM, × 10 500). (f) All satellite cells, active and quiescent, express m-cadherin (red cell membrane staining, yellow arrows) but only activated satellite cells express myogenin (green nuclear staining, white arrow). A blue nuclear dye was used as a counterstain for all nuclei. (confocal microscopy, magnification, × 400).
