Metachromatic leukodystrophy, juvenile form

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ORPHA:309263OMIM:250100E75.2
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Overview

Metachromatic leukodystrophy (MLD), juvenile form, is a rare inherited metabolic disease that damages the protective covering (called myelin) around nerve cells in the brain and throughout the body. It is caused by a shortage of an enzyme called arylsulfatase A (ARSA), which is needed to break down certain fatty substances called sulfatides. When sulfatides build up, they destroy the myelin sheath, leading to progressive loss of brain and nerve function. The juvenile form of MLD typically begins between the ages of 3 and 16 years. Early signs often include declining school performance, behavioral changes, difficulty walking, and clumsiness. Over time, children may lose the ability to walk, talk, and care for themselves. Seizures, vision problems, and difficulty swallowing can also develop as the disease progresses. The treatment landscape for juvenile MLD has improved in recent years. In 2024, the FDA approved atidarsagene autotemcel (Lenmeldy), a gene therapy, for pre-symptomatic or early symptomatic patients. Hematopoietic stem cell transplantation (bone marrow transplant) may also be considered in early stages. However, once significant neurological damage has occurred, treatment options are mainly supportive, focusing on managing symptoms and maintaining quality of life. Early diagnosis is therefore critical to access potentially disease-modifying treatments.

Also known as:

Key symptoms:

Declining school performanceBehavioral and personality changesDifficulty walking and frequent fallsClumsiness and poor coordinationSlurred speechDifficulty swallowingMuscle stiffness or spasticitySeizuresVision lossLoss of ability to speakIncontinence (loss of bladder or bowel control)Progressive intellectual declinePeripheral neuropathy (numbness or tingling in hands and feet)Loss of ability to sit or hold head up

Clinical phenotype terms (37)— hover any for plain English
LeukodystrophyHP:0002415Abnormal glycosphingolipid metabolismHP:0004343Abnormal social behaviorHP:0012433Punctate periventricular T2 hyperintense fociHP:0030081
Inheritance

Autosomal recessive

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

Age of Onset

Juvenile

Begins in the teen years

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for Metachromatic leukodystrophy, juvenile form.

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No actively recruiting trials found for Metachromatic leukodystrophy, juvenile form at this time.

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No specialists are currently listed for Metachromatic leukodystrophy, juvenile form.

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 Metachromatic leukodystrophy, juvenile form.

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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 stage is my child's disease at, and does that affect which treatments are available?,Is my child a candidate for gene therapy (Lenmeldy) or bone marrow transplant?,How quickly should we expect the disease to progress, and what milestones should we watch for?,Should other family members or future pregnancies be tested for MLD?,What therapies and support services should we start now to maintain my child's abilities as long as possible?,Are there any clinical trials currently enrolling patients with juvenile MLD?,What is the plan for managing symptoms like seizures, spasticity, and swallowing difficulties as they develop?

Common questions about Metachromatic leukodystrophy, juvenile form

What is Metachromatic leukodystrophy, juvenile form?

Metachromatic leukodystrophy (MLD), juvenile form, is a rare inherited metabolic disease that damages the protective covering (called myelin) around nerve cells in the brain and throughout the body. It is caused by a shortage of an enzyme called arylsulfatase A (ARSA), which is needed to break down certain fatty substances called sulfatides. When sulfatides build up, they destroy the myelin sheath, leading to progressive loss of brain and nerve function. The juvenile form of MLD typically begins between the ages of 3 and 16 years. Early signs often include declining school performance, behavi

How is Metachromatic leukodystrophy, juvenile form inherited?

Metachromatic leukodystrophy, juvenile form follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Metachromatic leukodystrophy, juvenile form typically begin?

Typical onset of Metachromatic leukodystrophy, juvenile form is juvenile. Age of onset can vary across affected individuals.