RARS-related autosomal recessive hypomyelinating leukodystrophy

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ORPHA:438114OMIM:616140E75.2
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Overview

RARS-related autosomal recessive hypomyelinating leukodystrophy, also known as DARS-related hypomyelinating leukodystrophy or sometimes referred to as hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL), is a very rare inherited brain disorder. It is caused by changes (mutations) in the DARS gene, which provides instructions for making an enzyme called aspartyl-tRNA synthetase. This enzyme is essential for building proteins in cells, particularly in the brain and spinal cord. When this enzyme does not work properly, the protective covering around nerve fibers (called myelin) does not form correctly — a process known as hypomyelination. Without adequate myelin, nerve signals cannot travel efficiently through the brain and spinal cord. The condition typically appears in infancy or early childhood. Children may show delayed motor development, difficulty walking, stiff legs (spasticity), and problems with coordination and balance. Some children also experience speech difficulties, tremors, and mild to moderate intellectual disability. Brain MRI scans characteristically show reduced or absent myelin, particularly in the brainstem and spinal cord. There is currently no cure for this condition. Treatment is supportive and focuses on managing symptoms such as spasticity, movement difficulties, and speech problems through physical therapy, occupational therapy, speech therapy, and medications to reduce muscle stiffness. The disease course varies, but many affected individuals experience a slowly progressive decline in motor function over time.

Key symptoms:

Delayed motor milestones such as sitting and walkingStiff legs (spasticity)Difficulty walking or inability to walk independentlyPoor coordination and balance (ataxia)Tremors or shaking movementsSpeech difficulties or delayed speechMild to moderate intellectual disabilityAbnormal eye movements (nystagmus)Difficulty swallowingMuscle weaknessLearning difficultiesProgressive loss of motor skillsAbnormal reflexes

Clinical phenotype terms (27)— hover any for plain English
Cerebral hypomyelinationHP:0006808Lower limb hypertoniaHP:0006895Progressive extrapyramidal movement disorderHP:0007153Developmental stagnationHP:0007281
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 RARS-related autosomal recessive hypomyelinating leukodystrophy.

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No actively recruiting trials found for RARS-related autosomal recessive hypomyelinating leukodystrophy at this time.

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No specialists are currently listed for RARS-related autosomal recessive hypomyelinating leukodystrophy.

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 RARS-related autosomal recessive hypomyelinating leukodystrophy.

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Community

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Caregiver Resources

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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 progression of my child's condition based on their specific genetic mutation?,What therapies should we start right away to help preserve motor function?,Are there any clinical trials or research studies my child might be eligible for?,How often should we schedule brain MRI scans to monitor the disease?,What signs should prompt us to seek emergency medical care?,Can you refer us to a specialized leukodystrophy center for comprehensive care?,What educational supports and accommodations should we request for school?

Common questions about RARS-related autosomal recessive hypomyelinating leukodystrophy

What is RARS-related autosomal recessive hypomyelinating leukodystrophy?

RARS-related autosomal recessive hypomyelinating leukodystrophy, also known as DARS-related hypomyelinating leukodystrophy or sometimes referred to as hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL), is a very rare inherited brain disorder. It is caused by changes (mutations) in the DARS gene, which provides instructions for making an enzyme called aspartyl-tRNA synthetase. This enzyme is essential for building proteins in cells, particularly in the brain and spinal cord. When this enzyme does not work properly, the protective covering around nerve fibers (

How is RARS-related autosomal recessive hypomyelinating leukodystrophy inherited?

RARS-related autosomal recessive hypomyelinating leukodystrophy follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does RARS-related autosomal recessive hypomyelinating leukodystrophy typically begin?

Typical onset of RARS-related autosomal recessive hypomyelinating leukodystrophy is infantile. Age of onset can vary across affected individuals.