| Entry |
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| Name |
GM2 gangliosidoses, including:
Tay-Sachs disease (type I);
Sandhoff disease (type II);
Tay-Sachs disease AB variant
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| Description |
GM2 gangliosidoses are a group of autosomal recessive lysosomal storage disorders caused by deficiency of beta-hexosaminiase or the noncatalytic GM2 activator in glycosphingolipid catabolism. The enzymatic defect results in the accumulation of GM2 ganglioside in neurons that mainly affects motor and spinocerebellar function. Mutations of the HEXA gene cause deficiency of the beta-hexosaminidase A and result in Tay-Sachs disease. Mutations of the HEXB gene, encoding the beta-subunit, cause deficiency of both enzymes (beta-hexosaminidase A and B), leading to Sandhoff disease. Deficiency of the GM2 activator protein, which mediates the interaction between the water-soluble beta-hexosaminidase A and GM2 ganglioside, causes the AB variant of GM2 gangliosidosis.
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| Category |
Inherited metabolic disease; Lysosomal storage disease; Nervous system disease
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| Pathway |
| Other glycan degradation | | Glycosaminoglycan degradation | | Glycosphingolipid biosynthesis - globo series | | Glycosphingolipid biosynthesis - ganglio series | | Lysosome |
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| Gene |
(Type I) HEXA; beta-hexosaminidase A [HSA: 3073] [KO: K12373]
(Type II) HEXB; beta-hexosaminidase B [HSA: 3074] [KO: K12373]
(AB variant) GM2A; ganglioside GM2 activator [HSA: 2760] [KO: K12383]
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| Marker |
Urine oligosaccharides
GM2 ganglioside [GL: G00109] [CPD: C04884]
keratan sulfate [CPD: C00573]
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| Drug |
Substrate reduction therapy
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| Other DBs |
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| Reference |
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| Authors |
Heese BA |
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| Title |
Current strategies in the management of lysosomal storage diseases. |
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| Journal |
Semin Pediatr Neurol 15:119-26 (2008) |
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| Reference |
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| Authors |
Kolter T, Sandhoff K |
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| Title |
Sphingolipid metabolism diseases. |
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| Journal |
Biochim Biophys Acta 1758:2057-79 (2006) |
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| Reference |
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| Authors |
Winchester B |
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| Title |
Lysosomal metabolism of glycoproteins. |
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| Journal |
Glycobiology 15:1R-15R (2005) |
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| Reference |
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| Authors |
Myerowitz R, Lawson D, Mizukami H, Mi Y, Tifft CJ, Proia RL |
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| Title |
Molecular pathophysiology in Tay-Sachs and Sandhoff diseases as revealed by gene expression profiling. |
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| Journal |
Hum Mol Genet 11:1343-50 (2002) |
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| Reference |
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| Authors |
Maegawa GH, Banwell BL, Blaser S, Sorge G, Toplak M, Ackerley C, Hawkins C, Hayes J, Clarke JT |
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| Title |
Substrate reduction therapy in juvenile GM2 gangliosidosis. |
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| Journal |
Mol Genet Metab 98:215-24 (2009) |
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