Details of Disease

General Information of Disease (ID: DISELKA4)

• Disease Name: Sandhoff disease
• Synonyms: total hexosaminidase deficiency; Sandhoff disease, infantile type; GM2-gangliosidosis, type 2; hexosaminidase A and B deficiency disease; Beta-hexosaminidase-beta-subunit deficiency; GM2 gangliosidosis, type 2; Sandhoff-Jatzkewitz-Pilz disease; GM2 gangliosidosis, 0 variant; Sandhoff disease, adult type; Hexosaminidases a and B deficiency; Sandhoff disease, juvenile type; Sandhoff Jatzkewitz disease; Sandhoff disease, infantile, juvenile, and adult forms; GM2 gangliosidosis 0 variant; Hexosaminidases A and B deficiency; Sandhoff disease
• Definition: Sandhoff disease is a lysosomal storage disorder from the GM2 gangliosidosis family and is characterized by central nervous system degeneration.
• Disease Hierarchy:
  DISSYRHC: Hereditary peripheral neuropathy
  DIS1L24B: Eye degenerative disorder
  DISPT716: GM2 gangliosidosis
  DISZSG9R: Cerebral lipidosis with dementia
  DISELKA4: Sandhoff disease
• Disease Identifiers:
  MONDO ID: MONDO_0010006
  MESH ID: D012497
  UMLS CUI: C0036161
  OMIM ID: 268800
  MedGen ID: 11313
  Orphanet ID: 796
  SNOMED CT ID: 23849003

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 2 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GM2A	TTGOFW6	Limited	Genetic Variation	[1]
HEXA	TTJI5JW	Strong	Genetic Variation	[2]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
HEXB	DE6AY40	Definitive	Autosomal recessive	[3]

This Disease Is Related to 8 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
HHEX	OTLIUVYX	Limited	Genetic Variation	[4]
NPC2	OTE9UEJC	Limited	Biomarker	[5]
NPTX1	OTKVHCV0	Limited	Biomarker	[6]
RPS27A	OTIIGGZ2	Limited	Altered Expression	[7]
SNCB	OTELSEK6	Limited	Biomarker	[8]
HEXD	OTTMQKLM	Strong	Genetic Variation	[9]
OGA	OT7ZBWT1	Strong	Genetic Variation	[10]
HEXB	OTROYLCR	Definitive	Autosomal recessive	[3]

References

• [1] The GM2 gangliosidoses databases: allelic variation at the HEXA, HEXB, and GM2A gene loci.Genet Med. 2000 Nov-Dec;2(6):319-27. doi: 10.1097/00125817-200011000-00003.
• [2] Knock-down of HEXA and HEXB genes correlate with the absence of the immunostimulatory function of HSC-derived dendritic cells.Cell Biochem Funct. 2012 Jan;30(1):61-8. doi: 10.1002/cbf.1819. Epub 2011 Oct 13.
• [3] 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.
• [4] Clinical,biochemical and molecular analysis of five Chinese patients with Sandhoff disease.Metab Brain Dis. 2016 Aug;31(4):861-7. doi: 10.1007/s11011-016-9819-9. Epub 2016 Mar 28.
• [5] Autophagy in Niemann-Pick C disease is dependent upon Beclin-1 and responsive to lipid trafficking defects.Hum Mol Genet. 2007 Jun 15;16(12):1495-503. doi: 10.1093/hmg/ddm100. Epub 2007 Apr 27.
• [6] 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.
• [7] Altered gene expression in cells from patients with lysosomal storage disorders suggests impairment of the ubiquitin pathway.Cell Death Differ. 2007 Mar;14(3):511-23. doi: 10.1038/sj.cdd.4402013. Epub 2006 Aug 4.
• [8] Neuronal and glial accumulation of alpha- and beta-synucleins in human lipidoses.Acta Neuropathol. 2007 Nov;114(5):481-9. doi: 10.1007/s00401-007-0264-z. Epub 2007 Jul 25.
• [9] Mucopolysaccharidosis-like phenotype in feline Sandhoff disease and partial correction after AAV gene therapy.Mol Genet Metab. 2015 Sep-Oct;116(1-2):80-7. doi: 10.1016/j.ymgme.2015.05.003. Epub 2015 May 8.
• [10] 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.