Gangliosidosis: A Brief Review Of Associated Neuropathology Essay

Gangliosidosis: A Brief Review Of Associated Neuropathology Gangliosidosis is a lysosomal storage disease which affects primarily the nervous system. This disease is the result of an autosomal recessive mutation which causes a lack or deficiency of an enzyme important in the metabolism of gangliosides. This deficient enzyme can vary depending on the type of mutation present causing either GM1 or GM2 gangliosidosis. Each of these will be discussed later, although the overall effects are similar. Increased amounts of gangliosides inside neurons leads to, often lethal, neurodegenerative disorders. TAY- SACHS One of the more common of these disorders is known as Tay--Sachs. Bernard Sachs was the first to describe the cellular morphological features of this disease, "distended cytoplasm of the neurons and ballooning of their dendrites". Later, in the 1930’s, the term ganglioside was used to describe the accumulating material in the neurons which was characteristic of the disease. Tay-Sachs is an infantile form of GM2 gangliosidosis most often found in Ashkenazi Jews. The rate of this disease is almost ten times higher in this population than in most others. Genetically, Tay-Sachs disease (TSD) is caused by a mutation at the alpha subunit locus. In Ashkenazi Jews the mutation is primarily found in two forms. The first is a 4 base pair insertion into exon 11, the other is a G-to-C transversion mutation in the intron 12 splice site. A separate mutation has been found in the Moroccan Jews, the deletion of a phenylalanine codon in the alpha subunit sequence. Recently, other mutations have been identified in these and other populations. In all cases, these mutations impair the alpha subunit of beta hexosaminidase A resulting... ...8. Drucker, L."Identification and Rapid Detection of Three Tay--Sachs Mutations in the Moroccan Jew Population." Am. J. Human Genetics. 1992; 51: 371-77. Fredrico, A. "The Clinical Aspect of Adult Hexosaminidase Deficiencies." Developmental Neuroscience. 1991; 13: 280-287 Fukumizu, M. "Tay-Sachs Disease: Progression of Changes on Neuroimaging in Four Cases." Neuroradiology. 1992; 34: 483-486. Gravel, R.A. "Biochemistry and Genetics of Tay-Sachs Disease." The Canadian Journal of Neurological Sciences. 1991; 18: 419-423. Maia, Maria. "Juvenile GM2 Variant B1: Clinical and Biochemical Study in Seven Patients." Neuropediatrics. 1990; 21: 18-23. Specola, N. "The Juvenile and Chronic Forms of GM2 Gangliosidosis." Neurology. 1990; 40: 145-150. Suzuki, K. "Neuropathology of Late Onset Gangliosidosis." Developmental Neuroscience. 1991;13: 205-10.