KEGG   DISEASE: Defects in the degradation of gangliosideHelp
H00426                      Disease                                

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]
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.
Inherited metabolic disease; Lysosomal storage disease; Nervous system disease
Human diseases [BR:br08402]
 Congenital disorders of metabolism
  Lysosomal storage diseases
   H00426  Defects in the degradation of ganglioside
Human diseases in ICD-10 classification [BR:br08403]
 4. Endocrine, nutritional and metabolic diseases (E00-E90)
  E70-E90  Metabolic disorders
   E75  Disorders of sphingolipid metabolism and other lipid storage disorders
    H00426  Defects in the degradation of ganglioside
BRITE hierarchy
Other glycan degradation
Glycosphingolipid biosynthesis - ganglio series
Glycosaminoglycan degradation
Sphingolipid metabolism
(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]
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]
Hematopoietic stem cell transplantation
Chemical chaperone therapy; N-octyl-4-epi-beta-valienamine (NOEV) (limited experience)
Enzyme replacement therapy, Gene therapy, Substrate reduction therapy (limited experience)
Hematopoietic stem cell transplantation
Enzyme-replacement therapy: Cerezyme [DR:D03020] Alglucerase [DR:D02810] Imiglucerase [DR:D03020]
Substrate reduction therapy: Miglustat, Zavesca [DR:D05032]
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
Heese BA
Current strategies in the management of lysosomal storage diseases.
Semin Pediatr Neurol 15:119-26 (2008)
PMID:19472408 (GM1)
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
GM1 gangliosidosis and Morquio B disease: expression analysis of missense mutations affecting the catalytic site of acid beta-galactosidase.
Hum Mutat 30:1214-21 (2009)
PMID:18202827 (GM1/ therapy)
Suzuki Y
Chemical chaperone therapy for GM1-gangliosidosis.
Cell Mol Life Sci 65:351-3 (2008)
PMID:12019216 (GM2)
Myerowitz R, Lawson D, Mizukami H, Mi Y, Tifft CJ, Proia RL
Molecular pathophysiology in Tay-Sachs and Sandhoff diseases as revealed by gene expression profiling.
Hum Mol Genet 11:1343-50 (2002)
PMID:16801539 (GM2)
Cachon-Gonzalez MB, Wang SZ, Lynch A, Ziegler R, Cheng SH, Cox TM
Effective gene therapy in an authentic model of Tay-Sachs-related diseases.
Proc Natl Acad Sci U S A 103:10373-8 (2006)
Maegawa GH, Banwell BL, Blaser S, Sorge G, Toplak M, Ackerley C, Hawkins C, Hayes J, Clarke JT
Substrate reduction therapy in juvenile GM2 gangliosidosis.
Mol Genet Metab 98:215-24 (2009)
PMID:18339196 (Gaucher)
Platt FM, Jeyakumar M
Substrate reduction therapy.
Acta Paediatr Suppl 97:88-93 (2008)

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