Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome

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ORPHA:314051OMIM:614924E88.8
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Overview

Leukoencephalopathy with thalamus and brainstem anomalies and high lactate syndrome (sometimes called LTBL) is an extremely rare genetic brain disorder. It affects the white matter of the brain (called leukoencephalopathy), along with specific structures including the thalamus and brainstem. The disease is caused by mutations in the EARS2 gene, which provides instructions for making an enzyme important for energy production inside the mitochondria — the power plants of our cells. When this enzyme does not work properly, cells cannot produce enough energy, leading to a buildup of lactic acid (lactate) in the body and brain. This condition typically appears in infancy. Affected babies may initially develop normally but then experience a decline in skills they had already learned, such as head control or the ability to sit. Common symptoms include muscle stiffness or weakness, developmental delays, difficulty feeding, and seizures. Brain MRI scans show characteristic abnormalities in the white matter, thalamus, and brainstem, and blood or spinal fluid tests often reveal elevated lactate levels. There is currently no cure for LTBL. Treatment is supportive and focuses on managing symptoms such as seizures, feeding difficulties, and movement problems. Some patients have a milder course with partial recovery after the initial decline, while others experience a more severe and progressive form. Research into mitochondrial diseases is ongoing, but specific therapies for this condition remain limited.

Also known as:

Key symptoms:

Developmental delay or regression (losing skills already learned)Muscle stiffness (spasticity)Muscle weaknessSeizuresDifficulty feeding or swallowingPoor head controlAbnormal eye movementsHigh levels of lactic acid in the bloodFailure to thrive or poor growthIrritabilityBreathing difficultiesInvoluntary muscle movements (dystonia)Intellectual disabilityVision problemsHearing 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 Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome.

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No actively recruiting trials found for Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome at this time.

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No specialists are currently listed for Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome.

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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 Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome.

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Community

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Latest news about Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome

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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.Does my child have the mild or severe form of LTBL, and what does that mean for their future?,What therapies should we start right away to support my child's development?,Are there any supplements or vitamins that might help with mitochondrial function?,What should we do if my child gets sick or has a fever to prevent worsening?,Are there any clinical trials or research studies we could participate in?,How often should we get brain MRI scans to monitor the condition?,What emergency signs should prompt us to go to the hospital immediately?

Common questions about Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome

What is Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome?

Leukoencephalopathy with thalamus and brainstem anomalies and high lactate syndrome (sometimes called LTBL) is an extremely rare genetic brain disorder. It affects the white matter of the brain (called leukoencephalopathy), along with specific structures including the thalamus and brainstem. The disease is caused by mutations in the EARS2 gene, which provides instructions for making an enzyme important for energy production inside the mitochondria — the power plants of our cells. When this enzyme does not work properly, cells cannot produce enough energy, leading to a buildup of lactic acid (l

How is Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome inherited?

Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome typically begin?

Typical onset of Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome is infantile. Age of onset can vary across affected individuals.