Metachromatic Leukodystrophy

Overview of Metachromatic Leukodystrophy

Enzymes are proteins that help break down (metabolize) substances in the body. If certain enzymes are not present, the body will be unable to metabolize a substance. If the substance remains in the body, it may build up. This can cause significant health complications.

Metachromatic leukodystrophy (MLD) occurs when an enzyme known as arylsulfatase A (ARSA) is not present in the body. ARSA breaks down fats known as sulfatides. Without ARA, sulfatides build up in cells, especially in the cells of the nervous system, causing damage to various organs, including the kidneys and nervous system (brain and spinal cord). These substances affect the nerves in the body, damaging them so that they are unable to send electrical impulses. Muscle weakness or lack of muscle control is common in patients with MLD and is a result of this type of damage to the nerves.

MLD is a rare disorder reported to occur in one in 40,000 to 160,000 worldwide, more in certain genetically isolated populations. MLD is passed down in families (inherited). Children must receive a gene from each parent to develop the disorder. Children who have only one gene for MLD are called carriers. Carriers are able to pass on the condition but do not have any symptoms of the disorder.

MLD is also known as

  • ARSA deficiency
  • arylsulfatase A deficiency disease
  • cerebral sclerosis, diffuse, metachromatic form
  • Greenfields disease
  • cerebroside sulphatase deficiency disease
  • metachromatic leukoencephalopathy
  • sulfatide lipidosis
  • sulfatidosis

Types of Metachromatic Leukodystrophy

There are three forms of MLD. Each form produces similar symptoms and is identified by the age at which symptoms develop. The three forms of MLD include:

  • late infantile MLD, which appears in children between 6 and 24 months of age
  • juvenile MLD, which appears in children between the ages of 4 and 12
  • adult MLD, which appears in teenagers or adults of any age

What Are the Symptoms of Metachromatic Leukodystrophy?

General symptoms of MLD that are seen in all three forms of the disease include:

  • abnormal muscle movement
  • behavior problems
  • decreased mental function
  • decreased muscle tone
  • difficulty walking
  • difficulty eating/feeding
  • frequent falls
  • incontinence
  • irritability
  • loss of muscle control
  • problems with nerve function
  • seizures
  • speech and swallowing difficulties

How Is Metachromatic Leukodystrophy Diagnosed?

Your doctor can make a diagnosis of MLD after conducting a physical exam and reviewing results from lab tests. If you have symptoms of MLD, your doctor may order a number of different tests to confirm your diagnosis, including the following:

Blood and Urine Tests

Your doctor will use blood tests to see if you have an enzyme deficiency. Urine tests will be used to see if you have a buildup of sulfatides.

Genetic Tests

Your doctor may order a genetic test to see if you have the gene that causes MLD.

Nerve Conduction Study

A nerve conduction study may be ordered to measure how the electrical impulses move through your nerves and muscles. This test can be used to measure nerve damage caused by MLD.


An MRI may be used to look at your brain. MLD causes the buildup of sulfatides in the brain. This can be seen on an MRI.

How Is Metachromatic Leukodystrophy Treated?

There is no cure for MLD. Treatment for the condition focuses on managing your symptoms and improving your quality of life. Your doctor may use several different treatments to help manage your symptoms:

  • medications to help control muscle movements and reduce pain
  • therapy to improve speech, muscle movements, and quality of life
  • nutritional assistance to cope with swallowing and eating difficulties

In some patients, a bone marrow or cord blood transplant may be effective for slowing the progression of the disease. When successful, the healthy cells received in the transplant can make the arylsulfatase A that the body was missing. Though this procedure will not reverse damage already done by the disease, it can stop future damage to the nervous system and prevent mental disability for some patients. This is most effective as an early intervention in patients who show few or no symptoms.

As with any medical procedure, there are risks associated with bone marrow transplant. The most common are:

  • graft-versus-host disease (GvHD): In some cases, the newly transplanted cells recognize the patients cells as invaders and try to attack them. GvHD may cause fever, rash, diarrhea, and sometimes damage to the liver or lungs. Treatment is with drugs that suppress the immune system. Treatment will stop the attack but will make you more susceptible to infection.
  • infection: Bone marrow transplant usually involves suppressing the immune system to prevent rejection of the transplanted cells. This increases your chances of developing an infection. It is important to treat any infection quickly so it does not develop into a more serious condition.

What Is the Long-Term Outlook for Patients With Metachromatic Leukodystrophy?

MLD is a progressive disease. This means that your symptoms will get worse over time. People who have the disease eventually lose all muscle and mental function. Your lifespan will be significantly shortened. Lifespan will depend on the age at which you were first diagnosed. The disease progresses more quickly when it is diagnosed at an early age. Children diagnosed with late infantile MLD typically live another five to 10 years. In juvenile MLD, life expectancy is 10 to 20 years after diagnosis. If symptoms do not appear until adulthood, you can expect to live 20 to 30 years following diagnosis.

How Can Metachromatic Leukodystrophy Be Prevented?

MLD is a genetic disorder that cannot be prevented. However, if the condition runs in your family, you may want to consider genetic testing and counseling to see if you are a carrier. Genetic counseling may help you to be better informed about the risks of passing the gene on to your children.