Metachromatic leukodystrophy

This rare genetic condition causes fatty substances to build up in the brain and nervous system. This results in loss of nerve function that worsens over time.

Update Date: 24.09.2026

Overview
Symptoms
When to see a doctor
Causes
Risk factors
Diagnosis
Treatment
Ongoing care
Potential future treatments
Coping and support
Preparing for your appointment
What you can do
What to expect from your doctor

By Mayo Clinic Staff

Overview

Metachromatic leukodystrophy (MLD) is a rare condition that causes fatty substances to build up in the brain and nervous system. These fatty substances are lipids called sulfatides. In MLD, the body doesn't make enough of a special enzyme to break down these sulfatides. Without this enzyme, sulfatides build up in the myelin covering that protects the nerve cells, damaging it. The damage causes the brain, spinal cord and nerves to lose function over time.

MLD is the result of a change in the ARSA gene. Most often, the changed gene is passed down by parents who have no symptoms. The child gets two copies of the changed gene, one from each parent, and has the condition.

There are three forms of MLD based on the age when symptoms start: late infantile form, juvenile form and adult form.

There is no cure for MLD yet. Depending on the form and age of onset, early diagnosis and treatment may help manage some symptoms and slow worsening of the condition.

Symptoms

Symptoms of metachromatic leukodystrophy include:

  • Delayed development or loss of motor skills, such as walking, moving, speaking, breathing and swallowing.
  • Stiff, rigid or weak muscles, trouble using muscles, and not being able to move.
  • Trouble feeling sensations, such as touch, pain and heat.
  • Gallbladder issues, including a higher risk of gallbladder cancer.
  • Weak eye muscles, eye movements that can't be controlled, vision loss and blindness.
  • Seizures.
  • Loss of bladder and bowel control.
  • Hearing loss.

Mental health symptoms include:

  • Trouble with thinking, remembering and learning.
  • Trouble sleeping.
  • Emotional issues, including irritability and mood disorders.
  • Behavioral issues, including personality changes, loss of skills and regression to less mature behavior.

The three forms of MLD can begin with different symptoms and vary in how quickly they worsen over time:

  • Late infantile form. This is the most common form. It worsens faster than the other forms. Symptoms start around 2 years of age or younger. Loss of speech and muscle function get worse quickly. Children with this form often do not live past childhood.
  • Juvenile form. This is the second most common form. It includes an early form that begins between ages 3 and 7 years and a late form that begins between 7 and 16 years. The early juvenile form generally has symptoms much like those of the late infantile form. Symptoms of the early juvenile form worsen faster than symptoms of the late juvenile form. The first symptoms of the late juvenile form often include behavioral changes, trouble with thinking and issues in school. Walking becomes hard in both forms. Children usually live less than 20 years after symptoms begin.
  • Adult form. This form is less common and usually starts after age 16. Symptoms begin slowly. They may include dementia symptoms, as well as behavioral issues, drug and alcohol misuse, and issues at school and work. Delusions and hallucinations may occur. Some people have periods when symptoms suddenly worsen. Adults may live for many years after symptoms start.

When to see a doctor

Talk with your healthcare professional if you or your child has symptoms that concern you.

Causes

Metachromatic leukodystrophy is caused by a changed gene that is passed from parents to children in an autosomal recessive pattern. This means that both parents have the changed gene, but they don't usually show symptoms of the condition. The child gets two copies of the changed gene, one from each parent, and has the condition. Sometimes the gene change happens by chance.

The most common cause of MLD is a change in the ARSA gene. This results in not having enough of the enzyme arylsulfatase A (ARSA) that breaks down lipids called sulfatides. Sulfatides build up in the myelin covering around the nerves. The buildup is toxic, destroying the myelin that protects the nerves. Over time, the damage affects how well the brain, spinal cord and nerves work.

Rarely, MLD is caused by a change in the PSAP gene. This gene change results in not having enough of a protein that stimulates ARSA to begin breaking down sulfatides. This also results in a buildup of sulfatides in the myelin covering around the nerves.

Risk factors

Children are at risk of metachromatic leukodystrophy if both parents carry a gene change known to cause the condition.

MLD happens more often in people with certain ancestry. Those at higher risk include Habbani Jews in Israel and members of the Navajo Nation in the U.S.

Diagnosis

To diagnose metachromatic leukodystrophy, a neurologist talks with you about symptoms and medical history. A neurologist is a doctor who specializes in the brain, spinal cord, nerves and muscles. A neurological exam checks how well different parts of the nervous system are working. The nervous system includes the brain, spinal cord and nerves. The nervous system sends signals that control muscles and other bodily functions.

Tests that help diagnose metachromatic leukodystrophy and how severe it is include:

  • Lab tests. Blood tests look at the level of ARSA enzyme activity. Urine tests can check sulfatide levels.
  • Genetic tests. You may be referred to a genetic counselor to learn about testing and what the test results mean for you. Genetic testing can look for the gene changes that cause MLD. Family members also may have genetic testing.
  • Nerve conduction study (NCS) and electromyogram (EMG). These tests measure electrical nerve impulses and function in muscles and nerves. During an NCS, a small current is passed through electrodes on the skin to check electrical signals. During an EMG, small needles are briefly inserted into muscles to record electrical activity. These tests can look for nerve damage, such as peripheral neuropathy, which is common with MLD.
  • Magnetic resonance imaging (MRI). This test uses a magnetic field and computer-generated radio waves to create detailed images of the brain. The test can look for a striped pattern of damaged myelin, also called white matter, in the brain.
  • Neuropsychometric testing. This testing can assess thinking, learning and changes in behavior. It may find the first signs in juvenile and adult forms of MLD.

Treatment

There is no cure for metachromatic leukodystrophy yet. Early treatment can help manage symptoms, prevent nerve damage, and stop or slow worsening of the condition. Early treatment also can help prevent complications and provide supportive care. Finding the condition early and getting early treatment may improve outcomes for some people with the condition.

Your healthcare team can work with you to help manage your symptoms over time. The goal is to improve quality of life.

MLD treatment can include:

  • Medicines. These may help lessen behavior and mood symptoms, seizures, and sleeping issues. They also may help lessen stomach and bowel issues, infection, and pain.

  • Gene therapy. The U.S. Food and Drug Administration approved a gene therapy for MLD called atidarsagene autotemcel (Lenmeldy). The healthcare team collects a person's own bone marrow stem cells and uses them to create the therapy. The goal is to replace the changed genes that caused MLD with healthy genes. This can stop the condition from getting worse or slow it down.

    The medicine is used for the late infantile form of MLD before symptoms begin. It also is used for the early juvenile form before symptoms begin or with early symptoms. Only one dose given by IV is needed, but it's expensive.

  • Bone marrow transplant. For some people with late juvenile and adult forms of MLD, allogenic bone marrow transplant is an option. Also called an allogeneic stem cell transplant, this procedure uses healthy blood stem cells from a donor to replace bone marrow that's not making enough healthy blood cells. The transplant is done before symptoms begin or when there are early symptoms. It may prevent or lessen some symptoms.

Supportive care can include:

  • Therapies. Physical therapy can help keep muscles and joints flexible. Occupational therapy can help with movement of the arms, wrists and hands and with doing daily care. Speech and language therapy can help with speaking, chewing and swallowing. As the condition worsens, a wheelchair or walker can be helpful. Devices to help with communication and self-care may be needed.
  • Feeding support. A dietitian can suggest ways to get extra nutrition when chewing and swallowing become difficult. Tube feeding, also known as enteral nutrition, may be an option. With this approach, a tube is passed through the belly and into the stomach for feeding.
  • Support for learning, mental health and behavior issues. Special services in school and talking with a mental health professional can help.
  • Other supports. You may need breathing help from a breathing machine. Long-term care may be an option. Palliative care can help. It's a specialized medical care that focuses on providing relief from pain and other symptoms of a serious illness.

Ongoing care

Care for MLD can be complex and change over time. Regular checkups with a team of medical professionals experienced in managing this condition may help prevent some complications. Talk with your healthcare professional about finding support at home, school or work.

Potential future treatments

Clinical trials hold promise for more treatment options beyond gene therapy currently available for the early-onset forms of MLD. Potential treatments being studied include:

  • Enzyme replacement or therapy to lower the buildup of lipids.
  • Substrate reduction therapy to lower the amount of lipids made.
  • Adding testing for MLD to standard newborn screening in the U.S. and other countries.

Talk to your healthcare professional about the possibility of participating in a clinical trial.

Coping and support

Caring for someone with metachromatic leukodystrophy can be challenging. More daily physical care may be needed as the condition worsens. You may not know what to expect, and you may worry about your ability to give the care needed.

To prepare yourself:

  • Learn about MLD. Learn as much as you can so that you can speak up about your needs and make good decisions about care.
  • Find a team of trusted professionals. They can help you make important decisions about care. Medical centers with specialty teams can offer you information about the condition, help arrange your care among specialists, help you look at care options and provide treatment.
  • Connect with others. Talking to people with the same kinds of challenges can give you tips and emotional support. Ask your healthcare team about support groups in your community. If a group setting isn't for you, maybe your team can put you in touch with a family who has someone with the same condition. Or you may be able to find group or individual support at a trusted site online.
  • Accept support. Asking for and accepting help in caring for your loved one can be difficult, but it is important. Ask about sources of short-term relief for primary caregivers, sometimes called respite care, and accept support from family and friends. Take time for your own interests and activities. Talk with a mental health professional if you need help adjusting and coping.

Preparing for your appointment

Make an appointment with your healthcare professional if you see symptoms that concern you. You may be referred to a doctor called a neurologist who specializes in evaluating and treating metachromatic leukodystrophy.

Here's some information to help you get ready for your appointment and what to expect from your healthcare professional.

What you can do

Before your appointment make a list of:

  • Any symptoms, including when they started and how they affect daily life.
  • All medicines, vitamins, herbs and supplements taken and the doses.
  • Questions to ask the healthcare professional.

Basic questions to ask may include:

  • What are the possible causes of these symptoms?
  • What kinds of tests are needed?
  • Should family members also be tested?
  • What treatments are available and which do you recommend?
  • Should I see a specialist?
  • What support services are available to help manage symptoms?
  • Are there print materials or websites that you'd suggest to help learn more about MLD?

Feel free to ask other questions during your appointment.

What to expect from your doctor

Your healthcare professional may ask:

  • Has anyone in your family ever had metachromatic leukodystrophy?
  • What are the symptoms and how do they affect daily life?
  • Has your child met developmental milestones, such as crawling, walking and talking?
  • Are there skills, such as talking and walking, you or your child could do before that can't be done now?
  • What, if anything, seems to make symptoms worse?
  • What, if anything, seems to make symptoms better?
  • Do you have concerns about life at home or going to school or work?
  • What medicines do you or does your child take?

Be ready to answer questions so that you have time to talk about what's most important to you.

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