Details of Disease

General Information of Disease (ID: DISWG5B4)

• Disease Name: Tay-sachs disease
• Synonyms: B variant GM2 gangliosidosis; GM2-gangliosidosis, variant B1; Tay-Sachs disease, variant B1; sphingolipidosis, Tay-Sachs; Tay-Sachs disease, juvenile; GM2-gangliosidosis, type 1; TSD; TAY-Sachs disease; B variant GM2-gangliosidosis; hexa deficiency; Tay-Sachs disease, pseudo-Ab variant; hexosaminidase alpha-subunit deficiency (variant B); hexosaminidase a deficiency; gangliosidosis GM2, type 1; GM2 gangliosidosis, type 1; GM2-gangliosidosis, adult chronic type; hexosaminidase a deficiency, adult type; disease, Tay-Sachs; Tay Sachs Disease; Tay-Sachs disease; Hex A pseudodeficiency; hexosaminidase A deficiency; GM2 gangliosidosis, B, B1 variant; GM2-gangliosidosis, several forms
• Disease Class: 5C56: Lysosomal disease
• Definition: GM2 gangliosidosis, variant B or Tay-Sachs disease is marked by accumulation of G2 gangliosides due to hexosaminidase A deficiency.
• Disease Hierarchy:
  DISSYRHC: Hereditary peripheral neuropathy
  DIS1L24B: Eye degenerative disorder
  DISPT716: GM2 gangliosidosis
  DISZSG9R: Cerebral lipidosis with dementia
  DISWG5B4: Tay-sachs disease
• ICD Code: ICD-11: ICD-11: 5C56.00
• Disease Identifiers:
  MONDO ID: MONDO_0010100
  MESH ID: D013661
  UMLS CUI: C0039373
  OMIM ID: 272800
  MedGen ID: 11713
  Orphanet ID: 845
  SNOMED CT ID: 111385000

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
AXO-AAV-GM2	DMISRRC	Phase 1	Gene therapy	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
FCGRT	TTKLPHO	Limited	Genetic Variation	[2]
ASPA	TT6TLZP	Strong	Genetic Variation	[3]
GM2A	TTGOFW6	Strong	Biomarker	[4]
HEXB	TTKIBKM	Strong	Genetic Variation	[5]
HEXA	TTJI5JW	Definitive	Autosomal recessive	[6]
HEXA	TTJI5JW	Definitive	CausalMutation	[7]

This Disease Is Related to 5 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
NPTX1	OTKVHCV0	Limited	Biomarker	[8]
HEXD	OTTMQKLM	moderate	Altered Expression	[9]
NEU3	OTQ5PQOW	moderate	Biomarker	[10]
HHEX	OTLIUVYX	Strong	Genetic Variation	[11]
HEXA	OT48T897	Definitive	Autosomal recessive	[6]

References

• [1] ClinicalTrials.gov (NCT04669535) A Two-Stage, Dose-Escalation and Safety & Efficacy Study of Bilateral Intraparenchymal Thalamic and Intracisternal/Intrathecal Administration of AXO-AAV-GM2 in Tay-Sachs or Sandhoff Disease. U.S.National Institutes of Health.
• [2] Tay-Sachs disease: intron 7 splice junction mutation in two Portuguese patients.Biochim Biophys Acta. 1995 Jan 25;1270(1):44-51. doi: 10.1016/0925-4439(94)00070-7.
• [3] Insights into the genetic epidemiology of Crohn's and rare diseases in the Ashkenazi Jewish population.PLoS Genet. 2018 May 24;14(5):e1007329. doi: 10.1371/journal.pgen.1007329. eCollection 2018 May.
• [4] Mutation in GM2A Leads to a Progressive Chorea-dementia Syndrome.Tremor Other Hyperkinet Mov (N Y). 2015 Jul 9;5:306. doi: 10.7916/D8D21WQ0. eCollection 2015.
• [5] GM2 gangliosidoses in Spain: analysis of the HEXA and HEXB genes in 34 Tay-Sachs and 14 Sandhoff patients.Gene. 2012 Sep 10;506(1):25-30. doi: 10.1016/j.gene.2012.06.080. Epub 2012 Jul 10.
• [6] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [7] Temporary Efficacy of Pyrimethamine in Juvenile-Onset Tay-Sachs Disease Caused by 2 Unreported HEXA Mutations in the Indian Population.Child Neurol Open. 2017 Jan 17;4:2329048X16687887. doi: 10.1177/2329048X16687887. eCollection 2017 Jan-Dec.
• [8] Neuronal pentraxin 1 depletion delays neurodegeneration and extends life in Sandhoff disease mice.Hum Mol Genet. 2017 Feb 15;26(4):661-673. doi: 10.1093/hmg/ddw422.
• [9] Splice junction mutation in some Ashkenazi Jews with Tay-Sachs disease: evidence against a single defect within this ethnic group.Proc Natl Acad Sci U S A. 1988 Jun;85(11):3955-9. doi: 10.1073/pnas.85.11.3955.
• [10] Murine Sialidase Neu3 facilitates GM2 degradation and bypass in mouse model of Tay-Sachs disease.Exp Neurol. 2018 Jan;299(Pt A):26-41. doi: 10.1016/j.expneurol.2017.09.012. Epub 2017 Sep 30.
• [11] A new point mutation (G412 to A) at the last nucleotide of exon 3 of hexosaminidase alpha-subunit gene affects splicing.Brain Dev. 2003 Apr;25(3):203-6. doi: 10.1016/s0387-7604(02)00219-x.