Epilepsy & Seizures
Epilepsy in infancy with migrating focal seizures
Jan. 14, 2023
At vero eos et accusamus et iusto odio dignissimos ducimus qui blanditiis praesentium voluptatum deleniti atque corrupti quos dolores et quas.
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:
Other symptoms may include:
Who 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:
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 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 using NIH 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.
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 visit NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with leukodystrophy at Clinicaltrials.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 Research
Canavan Foundation, Inc.
Canavan Research Foundation
Phone: 202-966-5557 or 800-336-4363
Global Dare Foundation (Adult Refsum Disease)
Hunter's Hope Foundation
Phone: 716-667-1200 or 877-984-4673
MLD Foundation (Metachromatic Leukodystrophy)
Phone: 800-617-8387 or 503-656-4808
Phone: 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 Association
Pelizaeus-Merzbacher Disease Foundation
United Leukodystrophy Foundation
Phone: 815-748-3211 or 800-728-5483
Information about leukodystrophy is also available:
Content source: https://www.ninds.nih.gov/health-information/disorders/leukodystrophy Accessed June 23, 2023.
The information in this document is for general educational purposes only. It is not intended to substitute for personalized professional advice. Although the information was obtained from sources believed to be reliable, MedLink, its representatives, and the providers of the information do not guarantee its accuracy and disclaim responsibility for adverse consequences resulting from its use. For further information, consult a physician and the organization referred to herein.