title: Adult GM2 gangliosidosis masquerading as slowly progressive muscular atrophy: motor neuron disease phenotype.
abstract: Ultrastructural and biochemical studies were performed on postmortem material of a 67-year-old woman presenting with proximal muscle weakness in the legs, slurred speech, and mental subnormality. The symptoms began at age 19 and showed extremely slow progression, mimicking progressive muscular dystrophy. A brother suffered from a similar chronic neuromuscular disease, and two sisters died at an early age from unknown "nervous" diseases. Autopsy disclosed abundant lipid accumulation in CNS neurons and severe cerebellar cortical atrophy of the granule cell type. Skeletal muscle showed a terminal stage of denervation atrophy with severe lipomatosis; intrafusal fibers of muscle spindles contained lipid deposits. Complex lamellar cytoplasmic inclusions often resembling membranous cytoplasmic bodies or stacked membranes were seen in cells of the brain. In addition, there were various lipopigment bodies, fingerprint profiles, rare polyglucosan bodies, rodlike structures, and filamentous sheaves, particularly in substantia nigra. Accumulation of gangliosides GM2 and GA2 in the cerebral cortex was demonstrated by thin-layer chromatography. Determination of hexosaminidase activity was not possible (formalin-fixed material). This observation, in addition to the cases reported by Navon et al. [1981] and Johnson [1982], is suggested to represent a new phenotype of adult-onset GM2 gangliosidosis referred to as motor neuron disease phenotype, which can be differentiated from other adult-onset lipidoses and motor neuron disorders. Our paper emphasizes the importance of ultrastructural demonstration of lamellar inclusions for the differential diagnosis of ceroid lipofuscinosis, and the value of biochemical studies in the diagnostic clarification of atypical neuromuscular disorders.
mesh_terms: D000328:Adult; D000368:Aged; D001284:Atrophy; D002525:Cerebellar Cortex / Q000473:pathology / Q000648:ultrastructure; D003937:Diagnosis, Differential; D005260:Female; D005625:Frontal Lobe / Q000032:analysis; D005732:Gangliosides / Q000032:analysis; D006801:Humans; D008854:Microscopy, Electron; D008875:Middle Aged; D009046:Motor Neurons / Q000473:pathology*; D009132:Muscles / Q000473:pathology; D009133:Muscular Atrophy / Q000175:diagnosis*; D010641:Phenotype; D012497:Sandhoff Disease / Q000175:diagnosis* / Q000235:genetics; D013378:Substantia Nigra / Q000473:pathology / Q000648:ultrastructure
chemical_list: D005732:Gangliosides