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Genetics Home Reference: your guide to understanding genetic conditions
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GM2-gangliosidosis, AB variant

Reviewed September 2008

What is GM2-gangliosidosis, AB variant?

GM2-gangliosidosis, AB variant is a rare inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord.

Signs and symptoms of the AB variant become apparent in infancy. Infants with this disorder typically appear normal until the age of 3 to 6 months, when their development slows and muscles used for movement weaken. Affected infants lose motor skills such as turning over, sitting, and crawling. They also develop an exaggerated startle reaction to loud noises. As the disease progresses, children with the AB variant experience seizures, vision and hearing loss, intellectual disability, and paralysis. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. Children with the AB variant usually live only into early childhood.

How common is GM2-gangliosidosis, AB variant?

The AB variant is extremely rare; only a few cases have been reported worldwide.

What genes are related to GM2-gangliosidosis, AB variant?

Mutations in the GM2A gene cause GM2-gangliosidosis, AB variant. The GM2A gene provides instructions for making a protein called the GM2 ganglioside activator. This protein is required for the normal function of an enzyme called beta-hexosaminidase A, which plays a critical role in the brain and spinal cord. Beta-hexosaminidase A and the GM2 ganglioside activator protein work together in lysosomes, which are structures in cells that break down toxic substances and act as recycling centers. Within lysosomes, the activator protein binds to a fatty substance called GM2 ganglioside and presents it to beta-hexosaminidase A to be broken down.

Mutations in the GM2A gene disrupt the activity of the GM2 ganglioside activator, which prevents beta-hexosaminidase A from breaking down GM2 ganglioside. As a result, this substance accumulates to toxic levels, particularly in neurons in the brain and spinal cord. Progressive damage caused by the buildup of GM2 ganglioside leads to the destruction of these neurons, which causes the signs and symptoms of the AB variant.

Because the AB variant impairs the function of a lysosomal enzyme and involves the buildup of GM2 ganglioside, this condition is sometimes referred to as a lysosomal storage disorder or a GM2-gangliosidosis.

Related Gene(s)

Changes in this gene are associated with GM2-gangliosidosis, AB variant.

  • GM2A

How do people inherit GM2-gangliosidosis, AB variant?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of GM2-gangliosidosis, AB variant?

These resources address the diagnosis or management of GM2-gangliosidosis, AB variant, and may include treatment providers.

  • Genetic Testing Registry: Tay-Sachs disease, variant AB (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268275)

You might also find information on the diagnosis or management of GM2-gangliosidosis, AB variant, in Educational resources (http://www.ghr.nlm.nih.gov/condition/gm2-gangliosidosis-ab-variant/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/gm2-gangliosidosis-ab-variant/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about GM2-gangliosidosis, AB variant?

You may find the following resources about GM2-gangliosidosis, AB variant, helpful. These materials are written for the general public.

  • MedlinePlus - Health information

    • Health Topic: Degenerative Nerve Diseases (http://www.nlm.nih.gov/medlineplus/degenerativenervediseases.html)
    • Health Topic: Tay-Sachs Disease (http://www.nlm.nih.gov/medlineplus/taysachsdisease.html)
  • Additional NIH Resources - National Institutes of Health
    National Institute of Neurological Disorders and Stroke: Lipid Storage Diseases Fact Sheet (http://www.ninds.nih.gov/disorders/lipid_storage_diseases/detail_lipid_storage_diseases.htm)
  • Educational resources - Information pages
    Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=845)

  • Patient support - For patients and families

    • Children Living with Inherited Metabolic Diseases (CLIMB) (UK) (http://www.climb.org.uk/)
    • Hide and Seek Foundation (http://hideandseek.org/Diseases.html)
    • National Organization for Rare Disorders (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/9/viewAbstract)
    • National Tay-Sachs and Allied Diseases Association (http://www.ntsad.org/)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Genetic Testing Registry - Repository of genetic test information

    • Genetic Testing Registry: Tay-Sachs disease, variant AB (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268275)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?cond=%22GM2-gangliosidosis%2C%20AB%20variant%22%20OR%20%22Gangliosidoses%20GM2%22%20OR%20%22Tay-Sachs%20Disease%2C%20AB%20Variant%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((ab%20variant%5BTIAB%5D%20AND%20gm2%5BTIAB%5D)%20OR%20(activator-deficient%20%5Btiab%5D%20AND%20tay-sachs%20disease%20%5Btiab%5D)%20OR%20(gm2%20activator%20deficiency%5BTIAB%5D)%20OR%20(ab%20variant%20%5Btiab%5D%20AND%20tay-sachs%20disease%20%5Btiab%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
  • OMIM - Genetic disorder catalog (http://omim.org/entry/272750)

What other names do people use for GM2-gangliosidosis, AB variant?

  • AB variant
  • Activator Deficiency/GM2 Gangliosidosis
  • Activator-deficient Tay-Sachs disease
  • GM2 Activator Deficiency Disease
  • GM2 gangliosidosis, type AB
  • Hexosaminidase activator deficiency
  • Tay-Sachs Disease, AB Variant

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about GM2-gangliosidosis, AB variant?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding GM2-gangliosidosis, AB variant?

autosomal ; autosomal recessive ; cell ; deficiency ; enzyme ; gene ; motor ; protein ; recessive ; toxic

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Chen B, Rigat B, Curry C, Mahuran DJ. Structure of the GM2A gene: identification of an exon 2 nonsense mutation and a naturally occurring transcript with an in-frame deletion of exon 2. Am J Hum Genet. 1999 Jul;65(1):77-87. (http://www.ncbi.nlm.nih.gov/pubmed/10364519?dopt=Abstract)
  • Mahuran DJ. Biochemical consequences of mutations causing the GM2 gangliosidoses. Biochim Biophys Acta. 1999 Oct 8;1455(2-3):105-38. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10571007?dopt=Abstract)
  • Sakuraba H, Itoh K, Shimmoto M, Utsumi K, Kase R, Hashimoto Y, Ozawa T, Ohwada Y, Imataka G, Eguchi M, Furukawa T, Schepers U, Sandhoff K. GM2 gangliosidosis AB variant: clinical and biochemical studies of a Japanese patient. Neurology. 1999 Jan 15;52(2):372-7. (http://www.ncbi.nlm.nih.gov/pubmed/9932959?dopt=Abstract)
  • Schepers U, Glombitza G, Lemm T, Hoffmann A, Chabas A, Ozand P, Sandhoff K. Molecular analysis of a GM2-activator deficiency in two patients with GM2-gangliosidosis AB variant. Am J Hum Genet. 1996 Nov;59(5):1048-56. (http://www.ncbi.nlm.nih.gov/pubmed/8900233?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: September 2008
Published: May 13, 2013