Gangliosidoses (Gangliosidosis)

A group of autosomal recessive lysosomal storage disorders marked by the accumulation of GANGLIOSIDES. They are caused by impaired enzymes or defective cofactors required for normal ganglioside degradation in the LYSOSOMES. Gangliosidoses are classified by the specific ganglioside accumulated in the defective degradation pathway.

Also Known As:

Networked: 139 relevant articles (1 outcomes, 11 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Mucopolysaccharidoses
2.	Tay-Sachs Disease
3.	Sandhoff Disease (Sandhoff's Disease)
4.	GM1 Gangliosidosis (Gangliosidosis GM1)
5.	Mucopolysaccharidosis IV (Morquio Syndrome)

Experts

1.	Whitley, Chester B: 5 articles (12/2021 - 02/2015)
2.	Platt, Frances M: 5 articles (01/2017 - 08/2003)
3.	Seyfried, Thomas N: 5 articles (09/2015 - 04/2007)
4.	Martin, Douglas R: 4 articles (01/2016 - 05/2004)
5.	Jeyakumar, Mylvaganam: 4 articles (06/2009 - 08/2003)
6.	Kim, Sarah: 3 articles (12/2021 - 09/2019)
7.	Jarnes-Utz, Jeanine R: 3 articles (12/2020 - 01/2018)
8.	Sandhoff, Konrad: 3 articles (04/2020 - 01/2012)
9.	Yamato, Osamu: 3 articles (03/2016 - 03/2006)
10.	Butters, Terry D: 3 articles (04/2010 - 08/2004)

Drugs and Biologics

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

1.	beta-Galactosidase (Lactaid)IBA 09/01/2008 - "Insights into post-translational processing of beta-galactosidase in an animal model resembling late infantile human G-gangliosidosis." 05/01/1987 - "Inactivation of GM1-ganglioside beta-galactosidase by a specific inhibitor: a model for ganglioside storage disease." 04/01/1986 - "The clinical symptoms, the complete deficiency of acidic beta-D-galactosidase and the storage products in visceral organs all suggest that this is a case of feline GM1-type gangliosidosis comparable with the severe infantile (Type 1) form of the disease in humans." 11/01/1981 - "Hepatic beta galactosidase and feline GMI gangliosidosis." 01/01/1979 - "The fused fibroblasts of infantile GMl-gangliosidosis and each of these adult patients had beta-galactosidase activity as expected for the average value in a mixture of equal numbers of parental cells. "
2.	GangliosidesIBA 05/01/1997 - "A previous study has demonstrated an unusual gangliosidosis in emu that is characterized by the accumulation of gangliosides in the brain tissues with GM3 and GM1 predominating. " 01/01/1979 - "Golgi and electron microscopic studies of neurons in human and feline ganglioside storage diseases indicate that ganglioside accumulation in cortical neurons initiates several complex alterations in neuronal geometry and morphology. " 05/01/2021 - "GMI gangliosidosis, associated with GMI ganglioside accumulation, is a neurodegenerative condition characterized by psychomotor regression, visceromegaly, cherry red spot, and facial and skeletal abnormalities. " 12/01/2020 - "The gangliosidoses are rare inherited diseases that result in pathologic accumulation of gangliosides in the central nervous system and other tissues, leading to severe and progressive neurological impairment and early death in the childhood forms. " 06/01/2016 - "The gangliosidoses are lysosomal storage disorders caused by accumulation of GM1 or GM2 gangliosides. "
3.	EnzymesIBA 11/28/2020 - "Subsequent analysis of 725 individuals showed clear discrimination of enzyme activities in patient samples (48 MLD; 21 gangliosidoses), with a sensitivity of 100% and specificity of 98-99%." 01/01/2019 - "Together, these results support the development of SRT for the treatment of gangliosidoses, particularly in patients with residual enzyme activity." 01/01/2013 - "All gangliosidoses are characterized by progressive neurodegeneration, the severity of which is proportional to the residual enzyme activity. " 09/01/1984 - "Gangliosidoses are very rare neurological diseases based on specific enzyme defects. " 01/01/1975 - "Different gene mutations in variants of GM1- and GM2- gangliosidosis demonstrated by enzyme analysis of (single) somatic hybrid cells."
4.	Hexosaminidases (Hexosaminidase)IBA 07/01/1980 - "Alpha-locus hexosaminidase genetic compound with juvenile gangliosidosis phenotype: clinical, genetic, and biochemical studies." 04/01/2003 - "The hexosaminidase (Hex) activities of 4 patients with GM(2) gangliosidosis were significantly decreased. " 09/20/2001 - "Mutations in the alpha-chain of lysosomal hexosaminidase (EC 3.2.1.52) underlie two distinct biochemical phenotypes known as variant B and variant B1 of G(M2) gangliosidosis. " 04/01/1974 - "These observations offer a genetic explanation for the biochemical and immunological relationships between hexosaminidases A and B and provide the framework for identifying the basic genetic defects responsible for GM(2) gangliosidosis." 01/01/2008 - "Sandhoff disease (gangliosidosis type 0) is a lysosomal storage disorder with a deficiency of hexosaminidases A and B. "
5.	Proteins (Proteins, Gene)FDA Link 08/01/2011 - "Lysosomal accumulation of Trk protein in brain of GM₁ -gangliosidosis mouse and its restoration by chemical chaperone." 05/01/2004 - "In this study, we determined that the causative mutation of G(M2) gangliosidosis in the domestic shorthair cat is a 25-base-pair inversion at the extreme 3' end of the beta-subunit (HEXB) coding sequence, which introduces three amino acid substitutions at the carboxyl terminus of the protein and a translational stop that is eight amino acids premature. " 01/01/2013 - "The gangliosidoses comprise a family of lysosomal storage diseases characterized by the accumulation of complex glycosphingolipids in the nervous system and other tissues, secondary to the deficient activity of lysosomal hydrolases or their associated activator proteins. " 01/01/1998 - "Mice with disrupted genes for activator proteins (SAP precursor -/-, GM2A -/-) as well as disrupted genes for ganglioside GM2 degrading hexosaminidases (HEXA -/-, HEXB -/-) turned out to be useful models for known human diseases whereas double knock out mice (HEXA -/- and HEXB -/-) show a new phenotype of both mucopolysaccharidosis and gangliosidosis." 01/01/2021 - "Gangliosidoses are inherited lysosomal storage disorders caused by reduced or absent activity of either a lysosomal enzyme involved in ganglioside catabolism, or an activator protein required for the proper activity of a ganglioside hydrolase, which results in the intra-lysosomal accumulation of undegraded metabolites. "
6.	ParaffinIBA 03/31/2016 - "The aim of the present study was to establish immunohistochemical and immunofluorescent techniques for the auxiliary diagnosis of canine and feline gangliosidoses, using paraffin-embedded brain specimens stored for a long period. " 01/01/1989 - "In the late infantile, infantile and Kufs variants studied in paraffin sections only, the GP component was detectable, too as in the case of the secondary neuronal LP in mucopolysaccharidoses and gangliosidoses. " 01/01/1989 - "In the late infantile, infantile and Kufs variants studied in paraffin sections only, the GP component was detectable, too as in the case of the secondary neuronal LP in mucopolysaccharidoses and gangliosidoses. "
7.	Galactose (Galactopyranose)FDA LinkGeneric 04/01/2006 - "We started this trial first in Fabry disease (generalized vasculopathy) using galactose and 1-deoxygalactonojirimycin, and then in beta-galactosidase deficiency disorders (beta-galactosidosis) with generalized neurosomatic and/or systemic skeletal manifestations (GM(1)-gangliosidosis and Morquio B disease), using a newly developed chemical compound N-octyl-4-epi-beta-valienamine (NOEV). " 10/11/2022 - "This article describes a case which seek medical advice for 2 months due to retrogressive development, The discovery of the characteristic fundus of the macular cherry-red spot is a key clue for further genetic analysis, GLB compound heterozygous mutations is detected, and enzymology results show that the acid B-galactose glucoside enzyme significantly decrease, fundus inspection help diagnosis GM1 gangliosidoses. "
8.	Amino AcidsFDA Link 01/01/1998 - "We identified a 1422 G-->C (amino acid W474C) substitution in the first position of exon 13 of HEXA of a non-Jewish proband who manifested a subacute variant of G(M2) gangliosidosis. " 05/01/2004 - "In this study, we determined that the causative mutation of G(M2) gangliosidosis in the domestic shorthair cat is a 25-base-pair inversion at the extreme 3' end of the beta-subunit (HEXB) coding sequence, which introduces three amino acid substitutions at the carboxyl terminus of the protein and a translational stop that is eight amino acids premature. "
9.	migalastatIBA 08/01/2004 - "The ability to escalate the dose of NB-DGJ, leading to extended life expectancy and increased delay in symptom onset, demonstrates the greater therapeutic potential of NB-DGJ for the treatment of the human gangliosidoses." 04/01/2006 - "We started this trial first in Fabry disease (generalized vasculopathy) using galactose and 1-deoxygalactonojirimycin, and then in beta-galactosidase deficiency disorders (beta-galactosidosis) with generalized neurosomatic and/or systemic skeletal manifestations (GM(1)-gangliosidosis and Morquio B disease), using a newly developed chemical compound N-octyl-4-epi-beta-valienamine (NOEV). "
10.	Neutral GlycosphingolipidsIBA 05/01/1997 - "To provide insight into this unique disorder of emu gangliosidosis, the current study focused on analysis of neutral glycosphingolipids and gangliosides from brain and liver tissues of affected birds and healthy controls. "

Therapies and Procedures

1.	Therapeutics 01/01/2013 - "There are no proven disease-modifying therapies for the gangliosidoses." 09/01/1975 - "At the present the gangliosidoses are not amenable to therapy. " 01/01/2018 - "Assessments by qMRI represent a robust non-invasive method for monitoring CNS changes in the clinical course of gangliosidoses and is ideally suited to monitor effects of novel CNS-directed therapies in future clinical trials." 01/01/2021 - "These successes could be the first of many more new gene therapies in development that mostly target loss-of-function mutation diseases with gene replacement (e.g., Batten disease, mucopolysaccharidoses, gangliosidoses) or, less frequently, gain-of-toxic-function mutation diseases by gene therapeutic silencing of pathologic genes (e.g., amyotrophic lateral sclerosis, Huntington's disease). " 10/01/2020 - "Substrate reduction therapy with Miglustat in pediatric patients with GM1 type 2 gangliosidosis delays neurological involvement: A multicenter experience."
2.	Deep Brain Stimulation 12/01/2006 - "Deep brain stimulation of the globus pallidus for generalized dystonia in GM1 Type 3 gangliosidosis: technical case report."
3.	Investigational Therapies (Experimental Therapy) 01/01/2016 - "Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. "
4.	Transplantation 04/01/2007 - "Intracranial transplantation of neural stem cells (NSCs) delayed disease onset, preserved motor function, reduced pathology and prolonged survival in a mouse model of Sandhoff disease, a lethal gangliosidosis. "
5.	Euthanasia (Mercy Killing) 10/01/1997 - "The mean age at which these affected emus were euthanatized, with distinct neurologic disease, or died was 5.7 mo. The second emu pair had 13 progeny, seven of which developed gangliosidosis, with a mean age of euthanasia/death of 4.6 mo. Affected emus died or were euthanatized from 2 to 8 mo of age. "