Details of Disease

General Information of Disease (ID: DISPT716)

• Disease Name: GM2 gangliosidosis
• Synonyms: GM2-gangliosidosis, B, B1, AB variant; GM>2< gangliosidosis; gangliosidosis GM2
• Disease Class: 5C56: Lysosomal disease
• Definition: 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.
• Disease Hierarchy:
  DISIHYU4: Gangliosidosis
  DISPN7D2: Inherited neurodegenerative disorder
  DISPT716: GM2 gangliosidosis
• ICD Code: ICD-11: ICD-11: 5C56.00
• Disease Identifiers:
  MONDO ID: MONDO_0017720
  MESH ID: D020143
  UMLS CUI: C0268274
  MedGen ID: 78656
  Orphanet ID: 309152
  SNOMED CT ID: 33316007

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
TSHA-101	DMFTPCT	Phase 1/2	Gene therapy	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 3 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
HEXB	TTKIBKM	moderate	Genetic Variation	[2]
CLN3	TTORF9W	Strong	Biomarker	[3]
GM2A	TTGOFW6	Strong	Genetic Variation	[4]

This Disease Is Related to 4 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
SYN1	OTMNPWC1	moderate	Biomarker	[5]
HHEX	OTLIUVYX	Strong	Genetic Variation	[6]
OGA	OT7ZBWT1	Strong	Biomarker	[7]
HEXD	OTTMQKLM	Definitive	Genetic Variation	[8]

References

• [1] ClinicalTrials.gov (NCT04798235) Phase 1/2, Open-Label Clinical Study to Evaluate the Safety and Efficacy of Intrathecal TSHA-101 Gene Therapy for Treatment of Infantile Onset GM2 Gangliosidosis. U.S.National Institutes of Health.
• [2] Novel bicistronic lentiviral vectors correct -Hexosaminidase deficiency in neural and hematopoietic stem cells and progeny: implications for in vivo and ex vivo gene therapy of GM2 gangliosidosis.Neurobiol Dis. 2020 Feb;134:104667. doi: 10.1016/j.nbd.2019.104667. Epub 2019 Nov 1.
• [3] Tripeptidyl-peptidase I in neuronal ceroid lipofuscinoses and other lysosomal storage disorders.Eur J Paediatr Neurol. 2001;5 Suppl A:73-9. doi: 10.1053/ejpn.2000.0439.
• [4] GM2 gangliosidosis AB variant: novel mutation from India - a case report with a review.BMC Pediatr. 2016 Jul 11;16:88. doi: 10.1186/s12887-016-0626-6.
• [5] Characterization of inducible models of Tay-Sachs and related disease.PLoS Genet. 2012 Sep;8(9):e1002943. doi: 10.1371/journal.pgen.1002943. Epub 2012 Sep 20.
• [6] Frequency of three Hex A mutant alleles among Jewish and non-Jewish carriers identified in a Tay-Sachs screening program.Am J Hum Genet. 1990 Oct;47(4):698-705.
• [7] Protease-resistant modified human -hexosaminidase B ameliorates symptoms in GM2 gangliosidosis model.J Clin Invest. 2016 May 2;126(5):1691-703. doi: 10.1172/JCI85300. Epub 2016 Mar 28.
• [8] Reversibility of neuropathology in Tay-Sachs-related diseases.Hum Mol Genet. 2014 Feb 1;23(3):730-48. doi: 10.1093/hmg/ddt459. Epub 2013 Sep 20.