Gregory M. Pastores, Gustavo H.B. Maegawa

Research output: Chapter in Book/Report/Conference proceedingChapter


GM2-gangliosidoses are neurodegenerative storage diseases, associated with intraneuronal GM2-ganglioside accumulation. Intralysosomal GM2-ganglioside hydrolysis requires the concerted action of β-hexosamidase A (HexA) and its cofactor GM2 activator protein. Thus, disease can occur as a consequence of mutations in either the gene which encodes subunits of HexA (α and β) or its cofactor, each of which is mapped to independent loci. There is significant overlap in clinical presentation among these three clinical subtypes, encompassing Tay-Sachs disease (α-mutations), Sandhoff disease (β-mutations), and the AB variant (cofactor defect), all of which are inherited in an autosomal recessive fashion. The majority of affected individuals display a rapid degenerative course in childhood, and there are late-onset forms associated with life extending into decades. Ongoing studies of underlying pathogenesis implicate neuroinflammatory processes. There are investigations of various therapeutic approaches, including substrate reduction therapy, the use of pharmacologic chaperones and gene therapy. However, no specific treatment has been introduced that has altered what is ultimately a poor prognosis. Prevention has been achieved through carrier testing in populations at risk and prenatal diagnosis.

Original languageEnglish (US)
Title of host publicationRosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease
Subtitle of host publicationFifth Edition
PublisherElsevier Inc.
Number of pages10
ISBN (Electronic)9780124105294
ISBN (Print)9780124105492
StatePublished - Nov 13 2014


  • G activator protein
  • G-gangliosidoses
  • Hexosamidase
  • Lysosomal storage disease
  • Sandhoff disease
  • Substrate reduction therapy
  • Tay-Sachs disease

ASJC Scopus subject areas

  • Medicine(all)


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