12/09/2004 Case 1: Fatal neonatal neuromuscular variant of glycogen branching enzyme deficiency

Clinical History:

This was a muscle biopsy from an infant girl born at 33 weeks gestation and found to have marked hypotonia with no spontaneous respiratory effort. She survived 41 days on ventilatory and other support; an EMG showed positive sharp waves and fibrillation, and this muscle biopsy was performed. After day 41 the supportive care was withdrawn and death followed.

Diagnostic Notes:

The circulated H&E slide of the biopsy showed muscle with preserved architecture. Some of the muscle fibers were regenerating, with large nucleoli and basophilic cytoplasm. There were some features suggestive of a neurogenic process such as some atrophic fibers, although all the fibers were of course small. However additionally some fibers had pale cytoplasmic inclusions (polyglucosan bodies) and large nuclei. It was demonstrated that the vacuoles/inclusions were PAS positive and that they resisted diastase predigestion. There was also strong staining with acid phosphatase. Electron microscopic examination showed lysosomal storage with polyglucosan-like
filaments, PLUS some membranous whorls and other storage material. Tissue sent for biochemical analysis in Dr DiMauro's laboratory had no detectable activity for brancher enzyme. The final diagnosis was one of "Fata~ Neonata~ Neuromuscu~ar Variant of G~ycoqen Brancher Enzyme Deficiency", a rare variant of this enzyme deficiency which is more commonly associated with adult polyglucosan body disease as well as some other childhood-onset conditions. Dr Hayes reviewed the biochemical pathways and the disorders of glycogen synthesis with neuropathological implications.

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