Overview
GM3 synthase deficiency is an extremely rare inherited metabolic disorder that affects the brain and nervous system. It is also known as Amish infantile epilepsy syndrome because it was first identified in the Old Order Amish community. The condition is caused by changes (mutations) in the ST3GAL5 gene, which provides instructions for making an enzyme called GM3 synthase. This enzyme is essential for producing certain complex fats called gangliosides, which play a critical role in brain development and function. Children with GM3 synthase deficiency typically appear normal at birth but begin showing symptoms in early infancy. The hallmark features include severe seizures (epilepsy) that are often difficult to control with medication, profound intellectual disability, and failure to reach developmental milestones such as sitting, walking, or speaking. Many children also develop abnormal involuntary movements, irritability, and problems with vision. Skin pigmentation changes, including darkening of the skin, have also been reported. There is currently no cure for GM3 synthase deficiency. Treatment is focused on managing symptoms, particularly controlling seizures with anti-epileptic medications, though seizures in this condition are often resistant to standard treatments. Supportive therapies such as physical therapy, occupational therapy, and nutritional support are important parts of care. Research into this condition is ongoing, but the rarity of the disease makes clinical trials challenging.
Also known as:
Key symptoms:
Severe seizures that are hard to controlProfound intellectual disabilityFailure to reach developmental milestonesInability to speakInability to walk independentlyIrritability and excessive cryingAbnormal involuntary movementsPoor muscle tone or stiffnessVision problemsSkin darkening or pigmentation changesFeeding difficultiesFailure to thriveDeafness or hearing loss
Autosomal recessive
Passed on when both parents carry the same gene change; often skips generations
Infantile
Begins in infancy, roughly 1 month to 2 years old
Treatments
No FDA-approved treatments are currently listed for GM3 synthase deficiency.
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Specialists
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Treatment Centers
8 centersBaylor College of Medicine Rare Disease Center ↗
Baylor College of Medicine
📍 Houston, TX
🏥 NORDStanford Medicine Rare Disease Center ↗
Stanford Medicine
📍 Stanford, CA
🔬 UDNNIH Clinical Center Undiagnosed Diseases Program ↗
National Institutes of Health
📍 Bethesda, MD
🔬 UDNUCLA UDN Clinical Site ↗
UCLA Health
📍 Los Angeles, CA
🔬 UDNBaylor College of Medicine UDN Clinical Site ↗
Baylor College of Medicine
📍 Houston, TX
🔬 UDNHarvard/MGH UDN Clinical Site ↗
Massachusetts General Hospital
📍 Boston, MA
🏥 NORDMayo Clinic Center for Individualized Medicine ↗
Mayo Clinic
📍 Rochester, MN
👤 Mayo Clinic Center for Individualized Medicine
🏥 NORDUCLA Rare Disease Day Program ↗
UCLA Health
📍 Los Angeles, CA
Travel Grants
No travel grants are currently matched to GM3 synthase deficiency.
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Caregiver Resources
NORD Caregiver Resources
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Mental Health Support
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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.What is the best combination of medications to control my child's seizures?,Would a ketogenic diet be appropriate for my child's epilepsy?,What developmental therapies should we start, and how often?,Are there any clinical trials or research studies my child might be eligible for?,What emergency plan should we have in place for prolonged seizures?,Should other family members be tested to see if they are carriers?,What specialists should be part of my child's care team?
Common questions about GM3 synthase deficiency
What is GM3 synthase deficiency?
GM3 synthase deficiency is an extremely rare inherited metabolic disorder that affects the brain and nervous system. It is also known as Amish infantile epilepsy syndrome because it was first identified in the Old Order Amish community. The condition is caused by changes (mutations) in the ST3GAL5 gene, which provides instructions for making an enzyme called GM3 synthase. This enzyme is essential for producing certain complex fats called gangliosides, which play a critical role in brain development and function. Children with GM3 synthase deficiency typically appear normal at birth but begin
How is GM3 synthase deficiency inherited?
GM3 synthase deficiency follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.
At what age does GM3 synthase deficiency typically begin?
Typical onset of GM3 synthase deficiency is infantile. Age of onset can vary across affected individuals.