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.

By Mayo Clinic Staff