Metachromatic Leukodystrophy

Enzymes are proteins that help break down, or metabolize, substances in the body. If certain enzymes aren’t 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) isn’t present in the body. ARSA breaks down fats known as sulfatides. Without ARSA, sulfatides build up in cells, especially in the cells of the nervous system, causing damage to various organs, including the kidneys and nervous system, which includes the brain and spinal cord. These substances affect the nerves in the body, damaging them so that they’re unable to send electrical impulses. Muscle weakness or lack of muscle control is common in people with MLD and is a result of this type of damage to the nerves.

MLD is a rare disorder that’s reported to occur in one in 40,000 to 160,000 people worldwide. This number is higher in certain genetically isolated populations. MLD is passed down in families, or 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 can pass on the condition but don’t have any symptoms of the disorder.

MLD is also known as:

  • ARSA deficiency
  • arylsulfatase A deficiency disease
  • cerebral sclerosis, diffuse, metachromatic form
  • Greenfield’s disease
  • cerebroside sulfatase deficiency disease
  • metachromatic leukoencephalopathy
  • sulfatide lipidosis
  • sulfatidosis

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 3 and 16 years old
  • adult MLD, which appears in teenagers or adults of any age

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 or feeding
  • frequent falls
  • incontinence
  • irritability
  • a loss of muscle control
  • problems with nerve function
  • seizures
  • difficulty speaking
  • difficulty swallowing

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 some tests to confirm your diagnosis, including the following:

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

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 people, a bone marrow or cord blood transplant may be effective in slowing the progression of the disease. When successful, the healthy cells received in the transplant can make the ARSA 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 people. This is most effective as an early intervention in people who show few or no symptoms.

As with any medical procedure, there are risks associated with bone marrow transplant. Risks associated with bone marrow transplant can be severe. The most common risks are graft-versus-host disease (GvHD) and rejection of the transplanted cells.

In some people, the newly transplanted cells recognize their cells as invaders and try to attack them. GvHD may cause:

  • a fever
  • a rash
  • diarrhea
  • liver damage
  • lung damage

The treatment for MLD includes drugs that suppress the immune system. The treatment will stop the attack but make you more likely to get an infection.

A 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’s important to treat any infection quickly to prevent it from developing into a more serious condition.

MLD is a progressive disease. This means that the symptoms tend get worse over time. People who have this disease lose all muscle and mental function eventually. Lifespan often depends on the age at which a person is first diagnosed.

The disease progresses more quickly when it’s diagnosed at an early age. Children diagnosed with late infantile MLD typically live another five to 10 years. In juvenile MLD, the life expectancy is 10 to 20 years after diagnosis. If the symptoms don’t appear until adulthood, people typically live 20 to 30 years after the diagnosis.

Although there’s still no cure for MLD, more treatments are being developed. Talk to your doctor about participating in clinical studies.

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’re a carrier. Genetic counseling may help you to be better informed about the risks of passing the gene on to your children.