GM2 gangliosidosis, AB variant

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ORPHA:309246OMIM:272750E75.0
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1Specialists8Treatment centers

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Overview

GM2 gangliosidosis, AB variant is an extremely rare inherited metabolic disease that affects the brain and nervous system. It is also sometimes called the GM2 activator deficiency or Tay-Sachs AB variant. In this condition, the body cannot properly break down a fatty substance called GM2 ganglioside, which builds up in nerve cells of the brain. Unlike the more well-known Tay-Sachs disease and Sandhoff disease (which are caused by problems with the enzymes themselves), the AB variant is caused by a missing or defective activator protein that the enzymes need to do their job. Without this activator protein, the GM2 ganglioside accumulates and progressively destroys nerve cells. The disease most commonly appears in infancy, usually between 3 and 6 months of age. Affected babies may initially develop normally but then begin to lose skills they had already learned, such as sitting, crawling, or babbling. Common symptoms include an exaggerated startle response to loud noises, progressive weakness, loss of vision, seizures, and severe intellectual disability. As the disease progresses, children lose the ability to move, swallow, and interact with their surroundings. Unfortunately, there is currently no cure or disease-modifying treatment for the AB variant of GM2 gangliosidosis. Care is focused on managing symptoms and keeping the child as comfortable as possible. This includes seizure management, nutritional support, respiratory care, and physical therapy. Research into potential therapies such as gene therapy and substrate reduction therapy is ongoing but remains in early stages.

Also known as:

Key symptoms:

Exaggerated startle response to loud soundsLoss of previously learned skills (developmental regression)Progressive muscle weaknessDifficulty swallowingSeizuresVision loss leading to blindnessCherry-red spot on the back of the eyeIncreasing stiffness or spasticity of musclesLoss of ability to sit, crawl, or moveIntellectual disabilityEnlarged head (macrocephaly) in some casesDecreased responsiveness to surroundingsFeeding difficultiesBreathing problems

Clinical phenotype terms (25)— hover any for plain English
NeurodegenerationHP:0002180Exaggerated startle responseHP:0002267Progressive spastic quadriplegiaHP:0002478HyperacusisHP:0010780Abnormal fear-induced behaviorHP:0100852Inappropriate behaviorHP:0000719Loss of speechHP:0002371Primitive reflexHP:0002476
Inheritance

Autosomal recessive

Passed on when both parents carry the same gene change; often skips generations

Age of Onset

Infantile

Begins in infancy, roughly 1 month to 2 years old

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for GM2 gangliosidosis, AB variant.

View clinical trials →

No actively recruiting trials found for GM2 gangliosidosis, AB variant at this time.

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Search ClinicalTrials.gov ↗Join the GM2 gangliosidosis, AB variant community →

Specialists

1 foundView all specialists →
JM
Joe TR Clarke, MD
Specialist
PI on 1 active trial

Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Travel Grants

No travel grants are currently matched to GM2 gangliosidosis, AB variant.

Search all travel grants →NORD Financial Assistance ↗

Community

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Latest news about GM2 gangliosidosis, AB variant

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Caregiver Resources

NORD Caregiver Resources

Support, advocacy, and financial assistance for caregivers of rare disease patients.

Mental Health Support

Rare disease caregiving can be isolating. Connect with counseling and peer support.

Family & Caregiver Grants

Financial assistance programs specifically for caregivers of rare disease patients.

Social Security Disability

Learn how rare disease patients may qualify for SSDI/SSI benefits.

Questions for your doctor

Bring these to your next appointment

  • Q1.How can we confirm that this is the AB variant specifically, and not Tay-Sachs or Sandhoff disease?,What symptoms should we expect to see next, and how can we prepare for them?,What is the best plan for managing seizures and feeding difficulties?,Are there any clinical trials or experimental treatments that our child might be eligible for?,Should other family members or future pregnancies be tested, and how does carrier testing work for this condition?,What palliative care and support services are available to help our family?,Can you connect us with other families affected by GM2 gangliosidosis for peer support?

Common questions about GM2 gangliosidosis, AB variant

What is GM2 gangliosidosis, AB variant?

GM2 gangliosidosis, AB variant is an extremely rare inherited metabolic disease that affects the brain and nervous system. It is also sometimes called the GM2 activator deficiency or Tay-Sachs AB variant. In this condition, the body cannot properly break down a fatty substance called GM2 ganglioside, which builds up in nerve cells of the brain. Unlike the more well-known Tay-Sachs disease and Sandhoff disease (which are caused by problems with the enzymes themselves), the AB variant is caused by a missing or defective activator protein that the enzymes need to do their job. Without this activa

How is GM2 gangliosidosis, AB variant inherited?

GM2 gangliosidosis, AB variant follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does GM2 gangliosidosis, AB variant typically begin?

Typical onset of GM2 gangliosidosis, AB variant is infantile. Age of onset can vary across affected individuals.

Which specialists treat GM2 gangliosidosis, AB variant?

1 specialists and care centers treating GM2 gangliosidosis, AB variant are listed on UniteRare, sourced from ClinicalTrials.gov principal investigators, published research, and the NPPES NPI registry.