U.S. flag
        An official website of the United States government
          Here’s how you know

      Official websites use .gov
                A
                .gov
                website belongs to an official government organization in the United States.
          Secure .gov websites use HTTPS
                A lock
                  (
                  
                  )
                   or
                  https://
                   means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.Search
                Menu
    
                      Información en Español
                      Search NINDSSearch NINDS
            

            Main navigation
  

        
              Health Information
                                     Toggle Health Information Dropdown
                                Disorders
                Clinical Trials
                Patient & Caregiver Education
                Public Education
                Support Resources
                Funding
                                     Toggle Funding Dropdown
                                Find Funding Opportunities
                About Funding
                Preparing Your Application
                After You Submit
                Determining Your Funding Likelihood
                Manage Your Award
                NINDS Small Business Program
                Training & Career Development
                Current Research
                                     Toggle Current Research Dropdown
                                Coronavirus and NINDS
                Focus on Disorders
                Focus on Tools & Topics
                Research Funded by NINDS
                Research at NINDS
                Scientific Resources
                Trans-Agency Activities
                News & Events
                                     Toggle News & Events Dropdown
                                Events
                News
                Director's Messages
                About NINDS
                                     Toggle About NINDS Dropdown
                                Who We Are
                What We Do
                Job Opportunities 
 Home
SHARE: Leukodystrophy
On this page

            What is leukodystrophy?

Leukodystrophy refers to genetic diseases that predominantly affect the white matter of the central nervous system (CNS). White matter is tissue made up of bundles of nerve fibers (axons) that connect nerve cells. The fibers are covered and protected by an insulating layer of proteins and fatty materials (lipids) called myelin. Myelin provides nutritional support to nerve cells and helps speed up signals between them, allowing them to send and receive messages quickly. It is also commonly referred to as the myelin sheath.

Leukodystrophy is not a single disorder. It is a group of rare, primarily inherited neurological disorders known as the leukodystrophies that result from the abnormal production, processing, or development of myelin and other components of CNS white matter, such as the cells called oligodendrocytes and astrocytes. Oligodendrocytes and astrocytes belong to a group of cells called glial cells which surround, support, and insulate nerve cells.

Leukodystrophies are usually progressive, meaning they get worse as time goes on. Some forms are present at birth, while others may not produce symptoms until a child becomes a toddler. A few leukodystrophies mostly affects adults.

**Symptoms of leukodystrophy**

Symptoms of leukodystrophy vary according to the specific type and may be difficult to recognize in the early stages of the disorder. Each type of leukodystrophy affects myelin differently and in different parts of the CNS, leading to a range of symptoms.

The most common symptom is a gradual functional decline in an infant or child who previously appeared well. Progressive loss may appear in:

muscle tone
	balance and mobility
	walking (gait)
	speech
	ability to eat
	vision
	hearing
	behaviorOther symptoms may include:

learning disabilities
	bladder issues
	breathing problems
	developmental delay
	muscle control disorders
	seizuresWho is more likely to get leukodystrophy?

All leukodystrophies are the result of genetic defects (mutations).

Myelin, which is whitish in color and makes up much of the white matter in the brain, is a complex substance made up of many different proteins and lipids (fatty substances). Production, degradation, and maintenance of each protein and lipid are controlled by a specific group of genes. Each type of leukodystrophy is caused by a defect in one of the genes that control the structure or amount of one of the proteins or lipids in myelin. Mutations in any of these genes can affect how the lipid or protein works and can interrupt the normal formation, processing, and development of myelin and the function of white matter. Damage to or destruction of myelin can slow or delay the speed of brain signals or keep them from reaching their destination.

**Types of leukodystrophy**

Scientists have identified more than 50 different leukodystrophies. Specific types include:

Alexander disease—a disorder characterized by the destruction of white matter and the formation of abnormal clumps of protein called Rosenthal fibers that accumulate in astrocytes in the brain. Alexander disease is caused by mutations in theGFAPgene.
	Autosomal dominant leukodystrophy with autonomic diseases (ADLD)—a rare, slowly progressive disorder characterized by the onset of autonomic dysfunction (dysfunction of the nerves that regulate nonvoluntary body functions, such as heart rate, blood pressure, and sweating), difficulty coordinating movements (ataxia), and mild cognitive impairment. People with ADLD develop symptoms in adulthood, usually in their 40s or 50s. The disorder is caused by mutations in the LMNB1 gene which is responsible for making lamin B1 protein. Lamin B1 is a structural protein that helps determine the shape of the cell nucleus and plays an important role in cell division and gene expression, including expression of the genes for oligodendrocyte development and production of some myelin proteins.
	Canavan disease—a neurological disorder in which the brain degenerates into spongy tissue full of small fluid-filled spaces. It is caused by a mutation in the ASPA gene which makes an enzyme called aspartoacylase. Aspartoacylase is primarily present in oligodendrocytes, contributes to the manufacture of myelin, and is responsible for breaking down (metabolizing) the brain chemical N-acetyl-L-aspartate or N-acetyl-L-aspartic acid.
	Cerebrotendinous xanthomatosis (CTX)—a rare, genetic disorder characterized by abnormal storage of fats (lipids) in many areas of the body. It affects the body's ability to metabolize fats, causing them to form fatty yellow nodules called xanthomas which accumulate in the body—especially in the brain, where abnormal giant cells filled with the fatty substance can be seen in the white matter, and the tendons that attach muscle to bone. CTX is caused by mutations in the sterol 27-hydroxylase (CYP27A1) gene. If diagnosed early, CTX can be effectively treated.
	Childhood ataxia with central nervous system hypomyelination or CACH (also called vanishing white matter disease or VWMD)—a disorder characterized by ataxia, muscle stiffness (spasticity), and damage to the optic nerve (optic atrophy). It is caused by mutations in any of the 5 genes that make the protein eukaryotic initiation factor 2B (eIF2B), which helps regulate protein synthesis, a process that governs the production of protein, including that which contributes to myelin, in cells. Mutations in any of these 5 genes results in partial loss of eIF2B function, making it difficult for cells to regulate protein synthesis.
	Krabbe disease, also called globoid cell leukodystrophy—a rare, inherited metabolic disorder characterized by globoid cells (abnormal cells that have more than one nucleus) in the white matter. Krabbe disease is caused by a defect in the GALC gene, leading to malfunction of galactocerebrosidase, an essential enzyme for myelin metabolism, and consequent accumulation of a toxic myelin breakdown product.
	Metachromatic leukodystrophy (MLD)—a disorder characterized by the toxic buildup of lipids and other storage materials in cells in CNS white matter and the peripheral nerves. Individuals with MLD have mutations in the ARSA or PSAP genes, which cause a deficiency of the enzyme arylsulfatase A and a decreased ability to break down sulfatides. Sulfatides are essential components of the myelin sheath. However, an excess of sulfatides can be toxic to the nervous system, gradually destroying myelin-producing cells and leading to nervous system impairment.
	Pelizaeus-Merzbacher disease—a rare, progressive, degenerative disorder in which coordination, motor abilities, and intellectual function deteriorate. It is caused by a mutation in the gene that controls the production of a myelin protein called proteolipid protein-1 (PLP1).
	Refsum disease:
	Adult Refsum disease (ARD)—a rare disease that causes weakness or numbness of the hands and feet (peripheral neuropathy). People with ARD lack the enzyme in peroxisomes that breaks down phytanic acid, a type of fat found in certain foods. Peroxisomes are cell structures required for the normal function of the brain, eyes, liver, kidney, and bone. In ARD, phytanic acid accumulates and is toxic to myelin.
		Infantile Refsum disease (IRD)—an inherited disorder that damages the white matter of the brain and affects motor movements.
		Although ARD and IRD have similar names, they are separate disorders caused by different defects in the PHYH or PEX7 genes which result in disruption of the breakdown of phytanic acid.There are many other leukodystrophies, and some are still unidentified.

How is leukodystrophy diagnosed and treated?

**Diagnosing leukodystrophy**

Generally, a diagnosis of leukodystrophy is made based on medical and family health history, physical and neurological examinations, imaging scans such as magnetic resonance imaging (MRI) or computed tomography (CT), and other laboratory tests.

However, even with the help of imaging, lab tests, and clinical observations, leukodystrophy can be difficult to diagnose. A physician will use other specialized tests such as DNA sequencing to check for genetic disorders. Whole-exome and whole-genome sequencing—tests that map out and analyze the genetic information contained in all of a person's genes—often are used to identify and pinpoint specific genetic defects.

Doctors still are finding new types of leukodystrophy and discovering forms that are difficult to precisely diagnose.

**Treating leukodystrophy**

Treatment for most types of leukodystrophy is symptomatic and supportive, and may include:

medications
	physical, occupational, and speech therapies
	nutritional, educational, and recreational programsMedications can be used to manage muscle tone, seizures, and spasticity. Physical, occupational, and speech therapies may improve mobility, function, and cognitive problems. Nutritional, educational, and recreational programs also may be helpful, depending on the needs of the individual.

Stem cell or bone marrow transplantation is showing promise for a few types of leukodystrophy.

One of the leukodystrophies is now a treatable disease. With an early accurate diagnosis, CTX can be effectively treated with chenodeoxycholic acid (CDCA) replacement therapy. CDCA helps the body metabolize or break down fats such as cholesterol and can slow or stop progression of the disease.

What are the latest updates on leukodystrophy?

The mission of the National Institute of Neurological Disorders and Stroke (NINDS) is to seek fundamental knowledge of the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. NINDS, a component of the National Institutes of Health (NIH), is the primary NIH organization for research on leukodystrophies.

NINDS, in collaboration with the NIH Office of Rare Diseases Research at the National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases, supports the Lysosomal Disease Network (LDN). LDN uses limited resources to create centers with expertise in lysosomal diseases to help solve major challenges in diagnosis, disease management, and therapy. Goals of LDN include clinical trial readiness, newborn screening, long-term outcomes, and global reach.

NINDS also supports researchers who are working with the Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN)—a consortium of scientists, industry stakeholders, and patient advocacy leaders that promotes advances in the diagnosis and treatment of leukodystrophies. GLIA-CTN supports the collection, analysis, and sharing of clinical data and biological specimens; educating clinicians; and training new researchers to pave the way for transformative therapeutic trials across the leukodystrophies.

NINDS-supported scientists are creating various animal models to gain a better understanding of the leukodystrophies and using the models to develop better, more effective therapies for these disorders.

Other investigators funded by NINDS are studying specific types of leukodystrophy. In one study, researchers are looking at the role of inflammation in Alexander disease to determine if it plays a role in causing disease progression and whether it could be a therapeutic target for treating the disease.

Another research project is studying the therapeutic impact of newly combined treatments using gene therapy, stem cell transplantation, and small molecule neuroprotection in people with Krabbe disease to reduce neuroinflammation, cell death, and neurodegeneration. The goal of this study is to develop safer and more effective treatments for the disorder.

Scientists supported by NINDS also are looking for ways to reduce the overproduction of the structural protein lamin B1 which is seen in ADLD in an effort to correct myelin abnormalities or halt disease progression.

In another NINDS-funded project, researchers are working to identify mutations in myelin protein that cause either Pelizaeus-Merzbacher disease or spastic paraplegia type 2—two x-linked leukodystrophies.

More information about leukodystrophy research supported by NINDS and other NIH Institutes and Centers may be found usingNIH RePORTER, a searchable database of current and past research projects supported by NIH and other Federal agencies. RePORTER also includes links to publications and resources from these projects.

file-medical

Learn About Clinical Trials

Clinical trials are studies that allow us to learn more about disorders and improve care. They can help connect patients with new and upcoming treatment options.

How can I or my loved one help improve care for people with leukodystrophy?

Consider participating in a clinical trial so clinicians and scientists can learn more about leukodystrophy. Clinical research uses human volunteers to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.

All types of volunteers are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.

For information about participating in clinical research visitNIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with leukodystrophy atClinicaltrials.gov, a searchable database of federal and private clinical studies.



Where can I find more information about leukodystrophy?

The following organizations and resources help individuals, families, friends, and caregivers of people living with leukodystrophy:

Canavan Disease ResearchPhone: 800-83-2194

Canavan Foundation, Inc.Phone:877-422-6282

Canavan Research FoundationPhone:203-240-2326

Genetic AlliancePhone:202-966-5557 or 800-336-4363

Global Dare Foundation(Adult Refsum Disease)

Hunter's Hope FoundationPhone:716-667-1200 or 877-984-4673

MLD Foundation(Metachromatic Leukodystrophy)
Phone: 800-617-8387 or 503-656-4808

Myelin ProjectPhone: 800-869-3546 or 310-459-1071

National Organization for Rare Disorders(NORD)
Phone: 203-744-0100 or 800-999-6673

National Tay-Sachs and Allied Diseases AssociationPhone: 617-227-4463

Pelizaeus-Merzbacher Disease FoundationPhone: 254-313-9107

United Leukodystrophy FoundationPhone: 815-748-3211 or 800-728-5483



**Information aboutleukodystrophy is also available:**

MedlinePlus

Genetic and Rare Diseases Information Center

Rare Diseases Clinical Research Network

PubMed

Learn about related topics

Alexander Disease
	Canavan Disease
	Krabbe Disease
	Metachromatic Leukodystrophy
	Pelizaeus-Merzbacher Disease
	Refsum Disease, Adult
	Refsum Disease, Infantile
book-open

Order publications from the NINDS Catalog

The NINDS Publication Catalog offers printed materials on neurological disorders for patients, health professionals, and the general public. All materials are free of charge, and a downloadable PDF version is also available for most publications. Health Information
  
    

    Disorders
                                                              
                    
                                      Glossary of Neurological Terms
    
            Order PublicationsClinical Trials
                                                              
                    
                                      Clinical Trials in the Spotlight
    
            Find NINDS Clinical TrialsPatient & Caregiver Education
                                                              
                    
                                      Brain Attack Coalition
    
            Brain DonationPublic Education
                                                              
                    
                                      Brain Basics
                                                              
                    
                                      Know Your Brain
    
            Understanding Sleep
    
            Preventing Stroke
    
            The Life and Death of a Neuron
    
            Genes and the BrainKnow Stroke
                                                              
                    
                                      Health Professionals
                                                              
                    
                                      NIH Stroke ScalePatients and Caregivers
    
            Researchers
    
            Shareable Resources
                                                              
                    
                                      Recursos en EspañolMigraine Trainer® App
                                                              
                    
                                      Migraine Trainer® Shareable ResourcesMind Your Risks®
    
            NINDS Brain Educational Resources
        
  
              
    
            Support Resources
                                                              
                    
                                      Patient Organizations
    
            Professional Societies
    
            Government Resources

Did you find the content you were looking for?
  Yes, I did find the content I was looking for



No, I did not find the content I was looking forPlease rate how easy it was to navigate the NINDS website
  Very easy to navigate



Easy to navigate



Neutral



Difficult to navigate



Very difficult to navigateThank you for letting us know! Any other feedback?Submit

This site is protected by reCAPTCHA and the Google Privacy Policyand Terms of Serviceapply.

      Last reviewed on November 28, 2023
        Contact Us
  

        
              Contact NINDS
                Visitor Information
        Related Sites
  

        
              Site Map
                National Institutes of Health
                Department of Health & Human Services
                USA.gov
        Policies
  

        
              Accessibility
                Freedom of Information Act
                Linking Policy
                Privacy Statement
                Vulnerability Disclosure Policy
Follow NINDS On Social Media
          
          National Institutes of Health (NIH)
          9000 Rockville Pike, Bethesda, MD, 20892