GM2 Gangliosidoses (GM2 Gangliosidosis)

A group of recessively inherited diseases characterized by the intralysosomal accumulation of G(M2) GANGLIOSIDE in the neuronal cells. Subtypes include mutations of enzymes in the BETA-N-ACETYLHEXOSAMINIDASES system or G(M2) ACTIVATOR PROTEIN leading to disruption of normal degradation of GANGLIOSIDES, a subclass of ACIDIC GLYCOSPHINGOLIPIDS.

Also Known As:

Networked: 186 relevant articles (4 outcomes, 12 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Hypokinesia (Bradykinesia)
2.	Gaucher Disease (Gaucher's Disease)
3.	Mannosidase Deficiency Diseases (Mannosidosis)
4.	Sandhoff Disease (Sandhoff's Disease)
5.	GM1 Gangliosidosis (Gangliosidosis GM1)

Experts

1.	Tsuji, Daisuke: 7 articles (01/2013 - 08/2006)
2.	Itoh, Kohji: 6 articles (10/2011 - 08/2006)
3.	Sakuraba, Hitoshi: 6 articles (06/2011 - 01/2002)
4.	Cox, Timothy M: 4 articles (09/2012 - 06/2009)
5.	Matsuoka, Kazuhiko: 4 articles (10/2011 - 03/2007)
6.	Clarke, Joe T R: 4 articles (01/2011 - 11/2006)
7.	Butters, Terry D: 4 articles (04/2010 - 08/2002)
8.	Sandhoff, Konrad: 4 articles (11/2009 - 08/2002)
9.	Platt, Frances M: 4 articles (06/2009 - 08/2002)
10.	Jeyakumar, Mylvaganam: 4 articles (06/2009 - 08/2002)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to GM2 Gangliosidoses:

1.	miglustat (Zavesca)FDA Link 06/01/2009 - "To evaluate the safety and efficacy of miglustat in patients with GM2 gangliosidosis. " 12/01/2010 - "It has been proposed that substrate reduction therapy using N-butyl-deoxynojirimycin (miglustat) may delay neurological progression, at least in late-onset forms of GM2 gangliosidosis. " 12/01/2010 - "Substrate reduction therapy with miglustat in chronic GM2 gangliosidosis type Sandhoff: results of a 3-year follow-up." 08/01/2009 - "Pharmacokinetics, safety and tolerability of miglustat in the treatment of pediatric patients with GM2 gangliosidosis." 03/01/2005 - "The results of ongoing clinical trials of miglustat in type 3 Gaucher disease, Niemann-Pick disease type C and GM2 gangliosidosis are eagerly awaited."
2.	Pyrimethamine (Daraprim)FDA Link 01/01/2011 - "The objectives of the present clinical trial were to establish the tolerability and efficacy of the treatment of late-onset GM2 gangliosidosis patients with escalating doses of pyrimethamine, to a maximum of 100 mg per day, administered orally in a single daily dose, over a 16-week period . " 01/01/2011 - "An open-label Phase I/II clinical trial of pyrimethamine for the treatment of patients affected with chronic GM2 gangliosidosis (Tay-Sachs or Sandhoff variants)." 03/23/2007 - "Pyrimethamine as a potential pharmacological chaperone for late-onset forms of GM2 gangliosidosis." 08/01/2014 - "Chaperone therapy for GM2 gangliosidosis: effects of pyrimethamine on β-hexosaminidase activity in Sandhoff fibroblasts." 01/01/2011 - "We concluded that pyrimethamine treatment enhances leukocyte Hex A activity in patients with late-onset GM2 gangliosidosis at doses lower than those associated with unacceptable side effects. "
3.	Levodopa (L Dopa)FDA LinkGeneric 11/01/2015 - "l-Dopa was started in four patients, leading to a significant improvement of hypokinesia in the patient suffering from GM2 gangliosidosis and a slight improvement in 3 unclassified patients. "
4.	Hexosaminidase A (Hex A)IBA 03/01/2008 - "GM2 gangliosidoses are a group of neuronal storage disorders caused by deficiency in the lysosomal enzyme hexosaminidase A. " 03/23/2007 - "We concluded that PYR functions as a mutation-specific PC, variably enhancing residual lysosomal Hex A levels in late-onset GM2 gangliosidosis patient cells." 06/06/1997 - "To confirm the relationship of the benign mutations and Hex A pseudodeficiency and to determine how the benign mutations reduce Hex A activity, we transiently expressed each of the benign mutations, and other mutations associated with infantile, juvenile, and adult onset forms of GM2 gangliosidosis, as Hex S (alphaalpha) and Hex A (alphabeta) in COS-7 cells. " 08/01/1996 - "Late-onset GM2 gangliosidosis: Ashkenazi Jewish family with an exon 5 mutation (Tyr180-->His) in the Hex A alpha-chain gene." 04/01/1995 - "GM2 gangliosidosis B1 variant: biochemical and molecular characterization of hexosaminidase A."
5.	Hexosaminidases (Hexosaminidase)IBA 01/01/2014 - "The GM2 gangliosidoses are a group of autosomal recessive lysosomal storage disorders caused by defective β-hexosaminidase. " 09/01/2012 - "Reversible transgenic expression of β-hexosaminidase directed by two promoters, mouse Hexb and human Synapsin 1 promoters, permitted progression of GM2 gangliosidosis in Sandhoff mice to be modified at pre-defined ages. " 11/15/2011 - "Using an authentic murine model of GM2 gangliosidosis, we examined the pattern of neuronal loss in the central nervous system and investigated the effects of gene transfer using recombinant adeno-associated viral vectors expressing β-hexosaminidase subunits (rAAV2/1-Hex). " 11/01/2011 - "G(M2) gangliosidoses are caused by an inherited deficiency of lysosomal β-hexosaminidase and result in ganglioside accumulation in the brain. " 06/01/2002 - "We investigated the alpha- and beta-subunits of beta-hexosaminidases in cultured fibroblasts from cases of various forms of GM2 gangliosidosis by means of Western blotting and a chemiluminescence detection system. "
6.	G(M2) Ganglioside (Ganglioside GM2)IBA 08/01/2007 - "M6PHexA was incorporated dose dependently into GM2 gangliosidosis patient-derived fibroblasts via M6P receptors on the cell surface, and degradation of accumulated GM2 ganglioside was observed." 11/01/2004 - "The GM2 gangliosidoses are caused by incomplete catabolism of GM2 ganglioside in the lysosome, leading to progressive storage and a neurodegenerative clinical course. " 06/01/2002 - "The GM2 gangliosidoses are a group of genetic disorders caused by the accumulation of ganglioside GM2 in neuronal cells. " 11/01/2000 - "The GM2 gangliosidoses are a group of recessive disorders characterized by accumulation of GM2 ganglioside in neuronal cells. " 06/03/1985 - "Ganglioside GM2, 3H-labeled in the sphingoid base, was added to the culture medium of normal and GM2 gangliosidosis fibroblasts. "
7.	OligosaccharidesIBA 11/15/1977 - "Structure of seven oligosaccharides excreted in the urine of a patient with Sandhoff's disease (GM2 gangliosidosis-variant O)." 11/15/1977 - "The urine of a patient with Sandhoff's disease (GM2 gangliosidosis-variant O) contains 10--12 N-acetylglucosamine-rich oligosaccharides in high amounts. " 09/01/1984 - "GM1 and GM2 gangliosidoses are progressive neurodegenerative diseases which accumulate intralysosomal gangliosides--and to a lesser extent oligosaccharides--chiefly in the central and peripheral nervous system owing to deficiencies of beta-galactosidase and hexosaminidases A or/and B, respectively. " 10/01/2005 - "Disease-specific oligosaccharides were identified for several oligosaccharidurias, including GM1 gangliosidosis, GM2 gangliosidosis, sialic acid storage disease, sialidase/neuraminidase deficiency, galactosialidosis, I-cell disease, fucosidosis, Pompe and Gaucher diseases, and alpha-mannosidosis. " 01/01/1987 - "Ricinus communis agglutinin-I (RCA-I) stained the glomerular epithelium only in GM1 and MPS-I. Succinylated wheat germ agglutinin (SWGA) stained the glomerular endothelium and epithelium in mannosidosis, and the glomerular epithelium and Bowman's capsule in MPS-I. Ultrastructure studies demonstrated an accumulation of oligosaccharides in cases of mannosidosis and GM1 gangliosidosis, a mixture of oligosaccharides and lipids in MPS-I, MPS-VI and GM2 gangliosidosis and only lipid storage in sphingomyelin lipidosis. "
8.	CeroidIBA 03/01/1987 - "In 20 cases they were abnormal (8 mucopolysaccharidosis, 6 GM1 gangliosidosis, 4 infantile neuroaxonal dystrophy, 1 GM2 gangliosidosis, 1 late infantile ceroid lipofuscinosis). " 01/01/1990 - "The data suggest that mucopolysaccharidosis (MPS) type IVA (Morquio disease), multiple sulphatase deficiency, Niemann-Pick disease type B, GM2 gangliosidosis type '0' (Sandhoff disease), and ceroid lipofuscinosis (Jansky-Bielschowsky and Batten-Spielmeyer-Vogt syndromes) are encountered frequently in Saudi Arabia, as compared to other storage diseases. " 10/01/2007 - "Lysosomal diseases were classified into 3 groups: (1) leukodystrophies (metachromatic leukodystrophy, Krabbe's disease and Salla's disease); (2) Neurodegenerative or psychiatric-like diseases (GM1 and GM2 gangliosidoses, Niemann Pick type C disease, sialidosis type I, ceroid-lipofuscinosis, mucopolysaccharidosis type III); (3) multisystemic diseases (Gaucher's disease, Fabry's disease, alpha and B mannosidosis, Niemann Pick disease type B, fucosidosis, Schindler/Kanzaki disease, and mucopolysaccharidosis type I and II. We propose a diagnostic approach guided by clinical examination, brain MRI, electrodiagnostic studies and abdominal echography."
9.	Messenger RNA (mRNA)IBA 10/08/1999 - "Studies of the biochemical impact of naturally occurring mutations associated with the GM2 gangliosidoses on mRNA splicing and stability, and on the intracellular transport and stability of the affected protein have provided some general insights into these complex cellular mechanisms. " 06/01/2004 - "Severe subacute GM2 gangliosidosis caused by an apparently silent HEXA mutation (V324V) that results in aberrant splicing and reduced HEXA mRNA."
10.	A-Form DNA (A-DNA)IBA 06/01/2007 - "Biochemical studies demonstrated that the kittens were affected with GM2 gangliosidosis variant 0, and a DNA assay finally demonstrated that these animals were homozygous for the mutation, which the authors had identified in a different family of the Japanese domestic cat. "

Therapies and Procedures

1.	Investigational Therapies (Experimental Therapy) 08/01/2014 - "This method may show promise for measuring the effectiveness of experimental therapies for GM2 gangliosidosis by allowing quantification of a reduction in the primary storage burden. "
2.	Enzyme Therapy 08/01/1979 - "Toward enzyme therapy in Gm2 gangliosidosis: beta-hexosaminidase infusion in normal cats."
3.	Enzyme Replacement Therapy 04/01/2011 - "Highly phosphomannosylated enzyme replacement therapy for GM2 gangliosidosis." 04/01/2011 - "Novel recombinant human lysosomal β-hexosaminidase A (HexA) was developed for enzyme replacement therapy (ERT) for Tay-Sachs and Sandhoff diseases, ie, autosomal recessive GM2 gangliosidoses, caused by HexA deficiency. "
4.	Bone Marrow Transplantation (Transplantation, Bone Marrow) 02/01/2000 - "Distribution of enzyme-bearing cells in GM2 gangliosidosis mice: regionally specific pattern of cellular infiltration following bone marrow transplantation." 02/01/2000 - "Tissue distribution of beta-hexosaminidase was investigated using 5-bromo-4-chloro-3-indolyl N-acetyl beta-D-glucosaminide (X-Hex) as substrate in wild-type mice, four GM2 gangliosidosis model mice (Hexa-/-, Hexb-/-, Gm2a-/- and Hexa-/-Hexb-/-) and Hexb-/- mice that received bone marrow transplantation (BMT). "
5.	Activator Appliances (Function Activator) 11/01/1993 - "The basis for the phenotype of GM2 gangliosidosis variant AB may therefore be either inactivation of the physiological activator function by the point mutation or instability of the mutant protein."