KEGG   DISEASE: H00426Help
Entry
H00426                      Disease                                

Name
Defects in the degradation of ganglioside, including:
GM1 gangliosidosis [DS:H00281];
Tay-Sachs disease (GM2 gangliosidoses type 1) [DS:H00124];
Sandhoff disease (GM2 gangliosidoses type 2) [DS:H00124];
Gaucher disease [DS:H00126]
Description
Defects in the degradation of ganglioside is a group of autosomal recessive lysosomal storage diseases caused by deficient activty of enzymes or their activators that play important roles in the degradation of ganglioside. The lack of a single enzyme leads to the complete blockage of the catabolic chain and results in the accumulation of undegraded substrates such as keratan sulfate, gangliosides, glucosylceramide and glycopeptides in neurons and skeletal tissues. Deficiency of the GM2 activator protein causes the AB variant of GM2 gangliosidosis. And saposin C is an activator of beta-glucocerebrosidase.
Category
Inherited metabolic disease; Lysosomal storage disease; Nervous system disease
BRITE hierarchy
Pathway
Other glycan degradation
Glycosphingolipid biosynthesis - ganglio series
Glycosaminoglycan degradation
Sphingolipid metabolism
Lysosome
Gene
(GM1) GLB1; beta-galactosidase [HSA:2720] [KO:K12309]
(GM2 type1) HEXA; beta-hexosaminidase A [HSA:3073] [KO:K12373]
(GM2 type2) HEXB; beta-hexosaminidase B [HSA:3074] [KO:K12373]
(GM2 AB variant) GM2A; ganglioside GM2 activator [HSA:2760] [KO:K12383]
(Gaucher) GBA; glucosylceramidase [HSA:2629] [KO:K01201]
(Gaucher) PSAP; prosaposin [HSA:5660] [KO:K12382]
Marker
Urine oligosaccharides
(GM1) GM1 ganglioside [GL:G00110] [CPD:C04911]
(GM2) GM2 ganglioside [GL:G00109] [CPD:C04884]
(GM1, GM2) keratan sulfate [CPD:C00573]
(GM1) Chondroitin sulfate [CPD:C00607]
(Gaucher) Glucocerebroside [GL:G10238] [CPD:C01190]
Drug
(GM1)
Hematopoietic stem cell transplantation
Chemical chaperone therapy; N-octyl-4-epi-beta-valienamine (NOEV) (limited experience)
(GM2)
Enzyme replacement therapy, Gene therapy, Substrate reduction therapy (limited experience)
(Gaucher)
Hematopoietic stem cell transplantation
Enzyme-replacement therapy: Cerezyme [DR:D03020] Alglucerase [DR:D02810] Imiglucerase [DR:D03020]
Substrate reduction therapy: Miglustat, Zavesca [DR:D05032]
Comment
Morquio syndrome B is non-neuronopathic form of GM1-gangliosidosis (see, H00123).
Some diseases are described as some phenotypes.
(GM1) Type 1: the severe infantile form. Type 2: the juvenile form. Type 3 the mild adult form
(Gaucher) Type 1: non-neuronopathic form. Type2: acute infantile neuropathic form. Type3: the chronic neuropathic form.
Other DBs
Reference
  Authors
Heese BA
  Title
Current strategies in the management of lysosomal storage diseases.
  Journal
Semin Pediatr Neurol 15:119-26 (2008)
Reference
PMID:19472408 (GM1)
  Authors
Hofer D, Paul K, Fantur K, Beck M, Burger F, Caillaud C, Fumic K, Ledvinova J, Lugowska A, Michelakakis H, Radeva B, Ramaswami U, Plecko B, Paschke E
  Title
GM1 gangliosidosis and Morquio B disease: expression analysis of missense mutations affecting the catalytic site of acid beta-galactosidase.
  Journal
Hum Mutat 30:1214-21 (2009)
Reference
PMID:18202827 (GM1/ therapy)
  Authors
Suzuki Y
  Title
Chemical chaperone therapy for GM1-gangliosidosis.
  Journal
Cell Mol Life Sci 65:351-3 (2008)
Reference
PMID:12019216 (GM2)
  Authors
Myerowitz R, Lawson D, Mizukami H, Mi Y, Tifft CJ, Proia RL
  Title
Molecular pathophysiology in Tay-Sachs and Sandhoff diseases as revealed by gene expression profiling.
  Journal
Hum Mol Genet 11:1343-50 (2002)
Reference
PMID:16801539 (GM2)
  Authors
Cachon-Gonzalez MB, Wang SZ, Lynch A, Ziegler R, Cheng SH, Cox TM
  Title
Effective gene therapy in an authentic model of Tay-Sachs-related diseases.
  Journal
Proc Natl Acad Sci U S A 103:10373-8 (2006)
Reference
  Authors
Maegawa GH, Banwell BL, Blaser S, Sorge G, Toplak M, Ackerley C, Hawkins C, Hayes J, Clarke JT
  Title
Substrate reduction therapy in juvenile GM2 gangliosidosis.
  Journal
Mol Genet Metab 98:215-24 (2009)
Reference
PMID:18339196 (Gaucher)
  Authors
Platt FM, Jeyakumar M
  Title
Substrate reduction therapy.
  Journal
Acta Paediatr Suppl 97:88-93 (2008)

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