Leukodystrophy: Symptoms, Causes, and Management

Medically reviewed by Dr. Baraa Alnahhal, MD · Last reviewed: October 2026

Leukodystrophy is a group of more than 50 rare, inherited neurological disorders that damage myelin, the protective covering of nerve cells in the brain and spine. The damage causes a progressive loss of neurological function that can affect movement, speech, vision, hearing, and thinking. The diseases are often fatal and have no cure, but symptoms can be treated, and gene therapy or stem cell transplants help in some types [1].

Quick Answer: What is leukodystrophy?

Leukodystrophy is a group of more than 50 rare, inherited neurological disorders that break down myelin, the protective coating around nerves in the brain and spinal cord. Each type stems from a different genetic mutation, and symptoms vary by type and age of onset. Diagnosis uses an exam, MRI and genetic testing. There is no cure, but treatments ease symptoms. [1]

What the research says

• MRI and genetic testing drive diagnosis. A review reports that MRI is the main diagnostic tool, that whole-exome sequencing has significantly improved the diagnostic yield, and that timely, accurate diagnosis is crucial for guiding symptomatic treatment and for judging eligibility for clinical trials (Ceravolo et al., J Neurol, 2024 [2]).

• Gene therapy preserved function in early cerebral adrenoleukodystrophy. In 17 boys with early-stage disease, 15 (88%) were alive and free of major functional disability, with minimal clinical symptoms, at the interim analysis (median follow-up 29.4 months); no treatment-related death or graft-versus-host disease was reported, but longer follow-up is needed (Eichler et al., N Engl J Med, 2017 [3]).

• Gene therapy helped children with early-onset metachromatic leukodystrophy, most when given before symptoms. In 29 treated children compared with 31 matched untreated children, 26 treated children were alive at a median of 3.16 years, and gross motor function scores 2 years after treatment were significantly higher (by 66% in late-infantile and 42% in early-juvenile disease); benefits were particularly clear in children treated before symptom onset (Fumagalli et al., Lancet, 2022 [4]).

What Is Leukodystrophy?

Leukodystrophy describes a group of more than 50 rare, inherited neurological disorders that primarily affect myelin, the protective covering on nerve cells in your brain and spine, also called white matter [1]. Myelin is essential for fast, efficient transmission of electrical signals through the nervous system.

In leukodystrophy, myelin is broken down. These diseases cause ongoing damage to myelin, which leads to a progressive (gradual) loss of neurological function in infants, children, and sometimes adults. The diseases are often fatal, but new therapies and clinical trials have shown promise [1].

A neuron with damaged myelin (left) compared with a healthy neuron (right): without intact myelin, nerve signals travel poorly.

What are the symptoms of leukodystrophy?

Symptoms vary widely between types and by the age at which they start, but most forms cause a gradual loss of neurological function. Not everyone has every symptom [1].

Affected function	Potential symptoms
Motor skills	Problems with balance, strength, movement, and coordination.
Senses	Changes in vision and hearing. Some types also cause neuropathy, which can bring numbness, tingling, and weakness.
Thinking and learning	Problems with learning, thinking, and remembering.
Physical health	Seizures, trouble eating and swallowing, and abnormal muscle tightness (spasticity) in some types.

Early symptoms depend on the type. For example, Krabbe disease often appears in infancy and can cause weakness, feeding difficulty, irritability, developmental delay, and seizures [1].

What are the genetic causes of leukodystrophy?

Leukodystrophy results from gene mutations in the genes that control the growth or function of myelin [1]. These mutations may be passed from parents to their biological children, but they may also happen randomly as cells grow and divide. You can carry a mutated gene without developing the disease, and carriers can still pass the gene on to their children [1].

Researchers have identified more than 50 types, and they are still finding new ones. Some examples include [1]:

• Adrenoleukodystrophy (ALD): affects the white matter of the brain and spinal cord and the adrenal glands, which control hormone production. Symptoms start in childhood or early adulthood.

• Krabbe disease (globoid cell leukodystrophy): symptoms often appear in infancy and can include weakness, feeding difficulty, irritability, developmental delay, neuropathy, and seizures.

• Metachromatic leukodystrophy: can appear in babies, children, or adults, with changes in thinking, behavior, vision, or hearing, seizures, neuropathy, dementia, and blindness.

• Alexander disease: causes developmental delays, seizures, and difficulty walking. It typically develops in newborns or children, though some types first show symptoms in adulthood.

If you carry a leukodystrophy gene mutation, you may want to consider genetic counseling. A genetic counselor reviews your biological family history and helps you understand your risk of passing the mutation to your children [1].

How is leukodystrophy diagnosed?

Even with testing, leukodystrophy is hard to diagnose because symptoms are wide-ranging, and many leukodystrophies go undiagnosed [1]. Providers use a combination of steps:

1. Evaluation and exams: a review of your symptoms and personal and biological family health history, plus a physical exam and a neurological exam.

2. Imaging: an MRI scan of the brain and spinal cord to check the white matter and look for myelin loss.

3. Genetic testing: blood and saliva tests to check for mutated genes in your DNA.

4. Newborn screening exams: may be part of the work-up in infants.

MRI is the main imaging tool for looking at the brain's white matter.

How is leukodystrophy managed and treated?

Leukodystrophy has no cure, but many of its symptoms can be treated to help people feel better and preserve some neurological function. Many symptoms can be treated to help you feel better and preserve some neurological function [1].

Supportive Therapies

• Medications: to manage seizures, muscle tightness, and movement problems.

• Therapy services: physical, occupational, and speech therapy for mobility, balance, speaking, and other skills.

• Nutritional support: nutritional therapy or feeding tubes for eating and swallowing problems.

• Hormone therapy: for adrenal gland dysfunction.

Advanced Medical Treatments

Gene therapy is a treatment available for some forms of leukodystrophy. It delivers genetic material to your cells and changes how they produce certain proteins [1]. A stem cell or bone marrow transplant may improve some types, but it is only helpful in rare cases, and chenodeoxycholic acid (CDCA) replacement therapy can treat cerebrotendinous xanthomatosis (CTX) if it is diagnosed early [1]. Several clinical trials are underway, so ask your provider whether a trial is an option for you or your child [1].

What is the bottom line on leukodystrophy?

Leukodystrophies are complex, life-altering disorders for patients and families. They are often fatal and progressive, and many children do not live past their early teens, but some people survive into adulthood, and new research and clinical trials are expanding the treatment options [1].

Care for leukodystrophy often involves a multidisciplinary team and genetic counseling.

Your next step: if you notice progressive neurological changes or developmental delays in your child, see a pediatric neurologist promptly. If leukodystrophy runs in your family, consider genetic counseling to understand your risk of passing the mutation on [1].

Frequently Asked Questions

What is leukodystrophy?

Leukodystrophy is a group of rare, inherited neurological disorders that cause the protective covering of nerves (myelin) in the brain and spine to break down [1].

How many types of leukodystrophy are there?

Researchers have identified more than 50 types, each caused by a different genetic mutation, and they are still discovering new forms [1].

Is leukodystrophy always fatal?

The diseases are often fatal, and many children with leukodystrophy die before their teenage years, though some people survive into adulthood. New treatments and clinical trials have offered hope for some people [1].

What are the most common symptoms?

Symptoms vary by type, but may include problems with balance, strength, movement and coordination, speech, eating and swallowing, hearing, vision, and thinking and memory [1].

Can adults develop leukodystrophy?

Yes. Many types start in infancy or childhood, but some, such as adult-onset autosomal-dominant leukodystrophy, appear in adulthood [1].

How is the condition diagnosed?

Providers review symptoms and family history and do a neurological exam. MRI of the brain and spine and genetic testing are key tests, and newborn screening exams may also be used [1].

Is there a cure for leukodystrophy?

There is no cure, but many symptoms can be treated, and gene therapy or a stem cell transplant helps some types [1].

What is the role of myelin?

Myelin is the protective coating around nerve cells. Without it, nerves can't communicate well, so the brain and body can't receive signals from each other [1].

Are these disorders contagious?

No. Leukodystrophies are genetic conditions and cannot be spread from person to person.

What advanced treatments are available?

For some types, gene therapy is available, and a stem cell or bone marrow transplant may help in rare cases. Clinical trials are underway for some forms [1][3][4].

References

1. Cleveland Clinic. Leukodystrophy. Cleveland Clinic. November 25, 2024. https://my.clevelandclinic.org/health/diseases/6034-leukodystrophy

2. Ceravolo G, Zhelcheska K, Squadrito V, et al. Update on leukodystrophies and developing trials. J Neurol. 2024;271(1):593-605. PMID 37755460. https://doi.org/10.1007/s00415-023-11996-5

3. Eichler F, Duncan C, Musolino PL, et al. Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy. N Engl J Med. 2017;377(17):1630-1638. PMID 28976817. https://doi.org/10.1056/NEJMoa1700554

4. Fumagalli F, Calbi V, Natali Sora MG, et al. Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access. Lancet. 2022;399(10322):372-383. PMID 35065785. https://doi.org/10.1016/S0140-6736(21)02017-1

Medical disclaimer

This article is for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. The clinical information in this guide reflects source material last reviewed in November 2024.