D,L-2-hydroxyglutaric aciduria

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ORPHA:356978OMIM:615182E72.8
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Overview

D,L-2-hydroxyglutaric aciduria (also called combined D-2- and L-2-hydroxyglutaric aciduria) is an extremely rare inherited metabolic disorder. In this condition, the body accumulates abnormally high levels of both D-2-hydroxyglutaric acid and L-2-hydroxyglutaric acid in the urine, blood, and spinal fluid. This happens because of a defect in a specific enzyme involved in processing these organic acids. The disease primarily affects the brain and nervous system, leading to severe developmental problems that usually begin in infancy or early childhood. Children with this condition typically experience severe developmental delay, seizures (epilepsy), low muscle tone (hypotonia) that may progress to increased muscle stiffness (spasticity), and intellectual disability. Brain imaging often shows abnormalities in the white matter of the brain, as well as changes in deeper brain structures. Some children may also have breathing difficulties and feeding problems. Currently, there is no cure for D,L-2-hydroxyglutaric aciduria. Treatment is supportive and focuses on managing symptoms such as seizures with anti-epileptic medications, physical therapy for movement difficulties, and nutritional support. Because this condition is so rare, research is limited, and families often benefit from connecting with metabolic disease specialists and rare disease support networks. Early diagnosis through metabolic testing and genetic analysis is important for appropriate management and family planning.

Also known as:

Key symptoms:

Severe developmental delayIntellectual disabilitySeizures or epilepsyLow muscle tone (floppiness) in infancyIncreased muscle stiffness over timeDifficulty feedingBreathing problemsAbnormal brain white matter on MRIPoor head controlDelayed or absent speechDelayed or absent ability to walkInvoluntary muscle movementsPoor growth or failure to thriveVision problems

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 D,L-2-hydroxyglutaric aciduria.

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No actively recruiting trials found for D,L-2-hydroxyglutaric aciduria at this time.

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Search ClinicalTrials.gov ↗Join the D,L-2-hydroxyglutaric aciduria community →

No specialists are currently listed for D,L-2-hydroxyglutaric aciduria.

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 D,L-2-hydroxyglutaric aciduria.

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Community

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Latest news about D,L-2-hydroxyglutaric aciduria

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Caregiver Resources

NORD Caregiver Resources

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

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 expected course of this disease for my child specifically?,What seizure medications are best suited, and what side effects should I watch for?,Are there any dietary changes or supplements that might help?,How often should brain MRI and metabolic testing be repeated?,Are there any clinical trials or research studies my child could participate in?,What therapies (physical, occupational, speech) do you recommend and how often?,Should other family members be tested as carriers of this condition?

Common questions about D,L-2-hydroxyglutaric aciduria

What is D,L-2-hydroxyglutaric aciduria?

D,L-2-hydroxyglutaric aciduria (also called combined D-2- and L-2-hydroxyglutaric aciduria) is an extremely rare inherited metabolic disorder. In this condition, the body accumulates abnormally high levels of both D-2-hydroxyglutaric acid and L-2-hydroxyglutaric acid in the urine, blood, and spinal fluid. This happens because of a defect in a specific enzyme involved in processing these organic acids. The disease primarily affects the brain and nervous system, leading to severe developmental problems that usually begin in infancy or early childhood. Children with this condition typically expe

How is D,L-2-hydroxyglutaric aciduria inherited?

D,L-2-hydroxyglutaric aciduria follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does D,L-2-hydroxyglutaric aciduria typically begin?

Typical onset of D,L-2-hydroxyglutaric aciduria is infantile. Age of onset can vary across affected individuals.