3-methylglutaconic aciduria type 3

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ORPHA:67047OMIM:258501E71.1
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Overview

3-methylglutaconic aciduria type 3, also known as Costeff syndrome or OPA3-related 3-methylglutaconic aciduria, is a rare inherited metabolic and neurological disorder. It is caused by changes in the OPA3 gene, which affects how cells produce and manage energy in their mitochondria — the tiny power plants inside every cell. When this gene does not work properly, a substance called 3-methylglutaconic acid builds up in the urine, and the brain and eyes are particularly affected. The most noticeable features of this condition are early vision loss caused by damage to the optic nerves (the nerves connecting the eyes to the brain), along with movement problems such as poor coordination, involuntary muscle movements (chorea), and stiffness. Many people also develop intellectual disability and some may have problems with their muscles or heart over time. Symptoms usually begin in early childhood. There is currently no cure for 3-methylglutaconic aciduria type 3. Treatment focuses on managing symptoms, supporting vision, and helping with movement and learning through therapies. Regular monitoring by a team of specialists is important to catch and manage complications early.

Also known as:

Key symptoms:

Progressive vision loss due to optic nerve damage (optic atrophy)Poor coordination and balance problems (ataxia)Involuntary, jerky or writhing movements (chorea)Muscle stiffness or spasticityIntellectual disability or learning difficultiesElevated levels of 3-methylglutaconic acid in the urineElevated levels of 3-methylglutaric acid in the urineSlurred or difficult speechWeakness in the arms and legsPossible heart muscle problems (cardiomyopathy) in some individuals

Clinical phenotype terms (9)— hover any for plain English
3-Methylglutaconic aciduriaHP:0003535
Inheritance

Autosomal recessive

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

Age of Onset

Childhood

Begins in childhood, roughly ages 1 to 12

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for 3-methylglutaconic aciduria type 3.

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No actively recruiting trials found for 3-methylglutaconic aciduria type 3 at this time.

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No specialists are currently listed for 3-methylglutaconic aciduria type 3.

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 3-methylglutaconic aciduria type 3.

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Community

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Caregiver Resources

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Questions for your doctor

Bring these to your next appointment

  • Q1.What specific OPA3 gene change has been found in my child, and what does it mean for their outlook?,How quickly is the vision loss likely to progress, and what vision aids or services should we access now?,Should other family members be tested to see if they are carriers of this condition?,What therapies — physiotherapy, occupational therapy, speech therapy — should my child start, and how often?,Does my child need heart monitoring, and how often should this be done?,Are there any clinical trials or research studies we could consider joining?,What support services and educational resources are available for children with this condition?

Common questions about 3-methylglutaconic aciduria type 3

What is 3-methylglutaconic aciduria type 3?

3-methylglutaconic aciduria type 3, also known as Costeff syndrome or OPA3-related 3-methylglutaconic aciduria, is a rare inherited metabolic and neurological disorder. It is caused by changes in the OPA3 gene, which affects how cells produce and manage energy in their mitochondria — the tiny power plants inside every cell. When this gene does not work properly, a substance called 3-methylglutaconic acid builds up in the urine, and the brain and eyes are particularly affected. The most noticeable features of this condition are early vision loss caused by damage to the optic nerves (the nerves

How is 3-methylglutaconic aciduria type 3 inherited?

3-methylglutaconic aciduria type 3 follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does 3-methylglutaconic aciduria type 3 typically begin?

Typical onset of 3-methylglutaconic aciduria type 3 is childhood. Age of onset can vary across affected individuals.