MEGDEL syndrome

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ORPHA:352328OMIM:614739E71.1
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Overview

MEGDEL syndrome, also known as 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, is a very rare inherited metabolic disorder. The name MEGDEL is an acronym that stands for its main features: 3-Methylglutaconic aciduria, Deafness, Encephalopathy, and Leigh-like syndrome. It is caused by mutations in the SERAC1 gene, which plays an important role in how cells handle certain fats (phospholipids) and produce energy in the mitochondria, the power plants of our cells. Babies with MEGDEL syndrome typically appear normal at birth but develop problems in the first days to months of life. Early signs often include feeding difficulties, low blood sugar, and liver problems in the newborn period. Over time, children develop progressive hearing loss (sensorineural deafness), movement problems including involuntary muscle contractions (dystonia), and intellectual disability. Brain imaging often shows changes similar to Leigh syndrome, a well-known mitochondrial disorder. A hallmark laboratory finding is elevated levels of 3-methylglutaconic acid in the urine. There is currently no cure for MEGDEL syndrome. Treatment is supportive and focuses on managing symptoms such as seizures, movement disorders, hearing loss (with hearing aids or cochlear implants), and nutritional support. A team of specialists including metabolic doctors, neurologists, and audiologists is essential. Research is ongoing to better understand the disease and develop potential therapies, but the condition remains progressive and significantly impacts quality of life.

Also known as:

Key symptoms:

Hearing loss (deafness) that worsens over timeInvoluntary muscle contractions and abnormal postures (dystonia)Intellectual disabilityFeeding difficulties in infancyLow blood sugar in the newborn periodLiver problems in early lifeSeizuresDelayed development or loss of previously learned skillsAbnormal brain changes seen on MRI (Leigh-like pattern)Elevated 3-methylglutaconic acid in urinePoor muscle tone (hypotonia) in infancySpasticity (stiff muscles) developing over timeDifficulty with balance and coordinationFailure to thrive or poor weight gainVisual problems

Inheritance

Autosomal recessive

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

Age of Onset

Neonatal

Begins at or shortly after birth (first 4 weeks)

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for MEGDEL syndrome.

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No actively recruiting trials found for MEGDEL syndrome at this time.

New trials open frequently. Follow this disease to get notified.

Search ClinicalTrials.gov ↗Join the MEGDEL syndrome community →

No specialists are currently listed for MEGDEL syndrome.

View NORD Rare Disease Centers ↗Undiagnosed Disease Network ↗

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 MEGDEL syndrome.

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Community

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Latest news about MEGDEL syndrome

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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.What is the expected course of MEGDEL syndrome for my child based on their current symptoms?,What therapies and interventions should we start right away to support development?,How should we manage feeding difficulties and ensure proper nutrition?,What should we do if my child has a seizure or a metabolic crisis at home?,Are there any clinical trials or research studies we could participate in?,How often should hearing, vision, and brain imaging be monitored?,What support services are available for our family, including respite care and counseling?

Common questions about MEGDEL syndrome

What is MEGDEL syndrome?

MEGDEL syndrome, also known as 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, is a very rare inherited metabolic disorder. The name MEGDEL is an acronym that stands for its main features: 3-Methylglutaconic aciduria, Deafness, Encephalopathy, and Leigh-like syndrome. It is caused by mutations in the SERAC1 gene, which plays an important role in how cells handle certain fats (phospholipids) and produce energy in the mitochondria, the power plants of our cells. Babies with MEGDEL syndrome typically appear normal at birth but develop problems in the first day

How is MEGDEL syndrome inherited?

MEGDEL syndrome follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does MEGDEL syndrome typically begin?

Typical onset of MEGDEL syndrome is neonatal. Age of onset can vary across affected individuals.