Ultrastructural abnormalities in the skeletal muscle of children with chronic cholestasis and a long-term vitamin E replacement.

We investigated the effects of long-term oral and intramuscular vitamin E repletion in children with chronic cholestasis. Clinical improvement or suppression of neuromuscular involvement after adequate vitamin E repletion was demonstrated. Light and electron microscopic abnormalities of the skeletal muscle, however, did not completely disappeared despite the correction of the biochemical abnormalities for more than 3 years. The muscle fibers showed less variety of pathologic features than before vitamin E repletion. Inclusions observed in the skeletal muscle fibers before vitamin E treatment were still observed in subsarcolemmal cytoplasm and the perinuclear regions. They were more irregularly curved and consisted of various substances. Similar inclusions were also observed in Schwann cells, perineural cells, fibroblasts, pericytes, endothelial cells and smooth muscle cells of intramuscular vessels. Although the external lamina was not disrupted, separation of the external lamina from the plasma membrane and multilayered external lamina were often observed. The nerves among muscle fibers still showed degenerative features. Morphological changes of the skeletal muscle during vitamin E therapy have not so far been reported in cases of chronic cholestasis. We discuss the relationship of these findings to vitamin E replacement in children with chronic cholestasis.