Massive Glycogen Accumulation Research Articles

Infantile acid maltase deficiency

In infantile acid maltase deficiency (AMD), masses of glycogen accumulate in muscle fibers and are then gradually digested. The metachromatic material found in some glycogen-filled fibers, not previously studied with the electron microscope, has two different fine structural appearances. Some is similar in shape and size to glycogen beta granules, but is more intensely stained, and some is in larger granules, irregular in shape, and has even higher stain affinity. Since acid maltase deficiency was identified by Hers, others have proposed that more than one genetic defect or additional extralysosomal factors are required to account for massive glycogen accumulation and metachromasia. There is no direct evidence of additional rare genetic defects. Presented herein are two simple proposals consistent with the primary deficiency. The first is that some partly digested glycogen is condensed and that this concentrates the sites that bind dye, producing metachromasia and other differences from normal glycogen. The second is that the massive accumulation of glycogen in muscle fibers involves, in addition to previously recognized lysosomal storage and lysosomal rupture, inactivation of sarcoplasmic phosphorylase caused by disruption of excitation-contraction linkages. These two proposals are physiologically plausible and potentially testable and do not invoke the coincidence of two or more rare genetic mutations.

Schwann cell changes and demyelination in chronic galactose neuropathy.

Dystrophic changes of Schwann cells and demyelination occurred in rats with chronic nerve edema induced by feeding a galactose-rich diet for two years. The mechanism for edema is the sorbitol pathway which generates osmotically active polyols from galactose or glucose. The blood-nerve barrier impedes diffusion of macromolecules from peripheral nerves, and endoneurial fluid pressure (EFP) becomes elevated. After 24-26 months of feeding with 40% galactose diet, myelinated nerve fibers showed segmental demyelination with bubbly disintegration of myelin sheaths, axonal degeneration, and remyelination. These pathologic changes were significantly more common than similar abnormalities in age-matched controls. Massive glycogen accumulation in Schwann cells, a unique morphologic finding, appeared only in experimental rats. Since edema and increased EFP are the earliest pathologic changes and are present for months before demonstrable nerve fiber injury, we suggest that they are responsible for the changes of myelinated fibers in chronic galactose neuropathy.

Electron microscope study of vitellogenesis in Glaridacris catostomi (Cestoidea: Caryophyllidea)

Swiderski Z. and Mackiewicz J. S. 1976. Electron microscope study of vitellogenesis in Glaridacris catostomi (Cestoidea: Caryophyllidea). International Journal for Parasitology 6: 61–73. Mature vitelline follicles consist of cells in various stages of development, progressing from immature cells of gonial type near the periphery to mature ones toward the centre. Maturation, completed before the cell leaves the follicle, is characterized by: increase in cell volume; increase in nuclear surface area restoring the N/C ratio; nucleolar transformation; extensive development of large parallel cisternae of granular endoplasmic reticulum, the shell-protein producing units; development of Golgi complexes engaged in shell globule formation; formation and storage of glycogen in the cytoplasm; simultaneous, independent formation and storage of intranuclear glycogen; progressive increase in the number and size of shell globule clusters; and disintegration of endoplasmic reticulum, degenerative changes, and accumulation of glycogen and shell globule clusters within the cytoplasm associated with a massive accumulation of glycogen in the nucleus. The functional significance of the large amount of nuclear and cytoplasmic glycogen and numerous shell globule clusters is analyzed. Vitellogenesis in G. catostomi is compared with that in other cestodes and trematodes. Some conclusions, concerning the interrelationship between the vitellogenesis pattern and the type of embryogenesis following it, are drawn and discussed.

Muscular abnormality in xeroderma pigmentosum: High resolution light-microscopy and electron-microscopic observations

Two cases of xeroderma pigmentosum and 1 case of the De Sanctis-Cacchione syndrome are presented. Muscle biopsies from all 3 patients showed identical alterations in 1 μ and 600 Å thin sections. The alterations consisted of massive accumulation of glycogen and subsarcolemmal mitochondrial aggregates. No similar lesion in muscle from xeroderma pigmentosum or the De Sanctis-Cacchione syndrome has been reported. A common aetiological mechanism is postulated for the muscle and skin lesions.

The myopathic variety of arthrogryposis multiplex congenita: A disorder with autosomal recessive inheritance

Two infants affected with the myopathic type of arthrogryposis multiplex congenita were studied. The muscle biopsies revealed similar light and electron microscopic changes in both patients, consisting of massive glycogen accumulation, disarray of myofilaments, and changes in mitochondria. All four parents of the two children are related to each other. Thus we propose that the myopathic type of arthrogryposis multiplex congenita is a specific genetic disease caused by a single gene and follows the autosomal recessive pattern of inheritance.