What is Metachromatic Leukodystrophy (MLD)

Metachromatic leukodystrophy is a genetic (inherited) disorder that causes a buildup of fatty substances (sulfatides) in the cells of the brain, spinal cord, nerves, liver, and kidneys.

This leads to a loss of mental and physical abilities that gradually gets worse. If you have MLD, it means your body is not producing enough of the protein needed to break down sulfatides and keep them from building up.

For most people, MLD starts between the ages of 1 and 4. In others, it develops in late childhood or in adulthood. There are four classifications of MLD, named for the age when signs and symptoms develop.

• Late infantile.
• Early juvenile.
• Late juvenile.
• Adult.

What are the causes?

MLD is caused by a defect in the ARSA gene (mutation). This gene is responsible for making an enzyme called arylsulfatase A (ASA) or sulfatide sulfatase. A mutation of the ARSA gene causes a deficiency of this enzyme. To develop MLD, you must inherit the gene mutation from both parents.

What increases the risk?

You are more likely to develop this condition if you are part of a specific ethnic group. These include:

• Habbanite Jews.
• Navajo people in the southwestern United States.
• Some Arab people who live in Israel.

What are the signs or symptoms?

Late infantile MLD begins before age 4.

• Children usually develop normally at first, but then start to have problems speaking and walking.
• Signs and symptoms get worse over several months.

Early and late juvenile MLD begins between the ages of 4 and 16.

• The first sign may be behavior or academic problems at school.
• Over time, difficulty walking, slurred speech, and seizures may develop.
• This form of the disease may progress more slowly than infantile MLD.

Adult MLD begins after age 16.

• Early signs may be a change in personality, mental health problems, and drug or alcohol abuse.
• This form may develop gradually over many years.
• It is the mildest form of MLD.

People with any form of MLD may eventually develop these signs and symptoms:

• Loose and weak muscles, or decreased muscle tone.
• Stiff and jerky muscles (spasticity).
• Crossed eyes and other abnormal eye movements.
• Loss of physical and mental ability.
• Clumsiness.
• Seizures.
• Complete loss of muscle use (paralysis).
• Blindness.

How is this diagnosed?

This condition may be diagnosed based on:

• Symptoms and medical history.
• Physical exam.
• Other tests, including:
  • A blood test to check for:
    • Low levels of the protein necessary to break down sulfatides.
    • The gene mutation.
  • A urine test to check for high levels of sulfatides.
  • MRI. This looks for changes in the brain.
  • A procedure to collect a sample of fluid from around the spine (spinal tap) to be tested for abnormal proteins.

How is this treated?

There is no cure for this condition. Treatment varies depending on your symptoms and how quickly the disease is progressing. Options may include:

• Physical therapy.
• Occupational therapy.
• Mental health therapy and support.
• Nutrition therapy.
• Speech therapy.
• Medicines to control seizures or to ease muscle spasms.
• Treatment for crossed eyes or loss of vision.

For some people, a bone marrow transplant (stem cell transplant) may slow the progression of the disease.

Follow these instructions at home:

General instructions

• Take over-the-counter and prescription medicines only as told by your health care provider.
• If you have MLD, talk to your family members about considering genetic testing to see if they carry the disease or may develop it in the future.
• If instructed, use assistive devices such as a cane, walker, splint, or brace. Follow your health care provider’s directions.
• Follow eating and drinking instructions given by your health care provider or a diet and nutrition specialist (dietitian).
• Work with a dietitian to maintain a healthy weight and to make sure you get enough protein in your diet.
• Do not use any products that contain nicotine or tobacco, such as cigarettes and e-cigarettes. If you need help quitting, ask your health care provider.
• Do not drink alcohol.
• Keep all follow-up visits as told by your health care provider. This is important. This includes any visits with physical, occupational, nutrition, or speech therapists.

Where to find more information

• The MLD Foundation: www.mldfoundation.org  

Contact a health care provider if you:

• Have new symptoms.
• Are not able to care for your medical needs at home.
• Have had a stem cell transplant and you also have:
  • Diarrhea.
  • Cough.
  • Nausea, vomiting, or loss of appetite.
  • Weakness or loss of energy.
  • Weight loss.
  • A skin rash.

Get help right away if you:

• Have a seizure.
• Develop paralysis.
• Have had a stem cell transplant and you also have:
  • Fever or chills.
  • Abnormal bleeding.
  • Very bad vomiting or diarrhea.
  • Very bad headache or confusion.
  • Trouble breathing.
  • Chest pain.

These symptoms may represent a serious problem that is an emergency. Do not wait to see if the symptoms will go away. Get medical help right away. Call your local emergency services (911 in the U.S.). Do not drive yourself to the hospital.

Summary

• Metachromatic leukodystrophy (MLD) is a genetic disorder that causes a buildup of fatty substances (sulfatides) in the cells of the brain, spinal cord, nerves, liver, and kidneys.
• This leads to a loss of mental and physical abilities that gradually gets worse.
• To develop MLD, you must inherit the gene mutation from both parents.
• There is no cure for this condition, and no treatment can reverse damage that is already done. Supportive care is an important part of MLD treatment.