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
have any symptoms of the disorder.
MLD is also known as:
- ARSA deficiency
- arylsulfatase A deficiency disease
- cerebral sclerosis, diffuse, metachromatic form
- cerebroside sulfatase deficiency disease
- metachromatic leukoencephalopathy
- sulfatide lipidosis
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 3 and 16 years old
- adult MLD, which appears in teenagers or adults of any
What Are the Symptoms of Metachromatic Leukodystrophy?
General symptoms of MLD that are seen in all three forms of the
- abnormal muscle movement
- behavior problems
- decreased mental function
- decreased muscle tone
- difficulty walking
- difficulty eating or feeding
- frequent falls
- a loss of muscle control
- problems with nerve function
- difficulty speaking
- difficulty swallowing
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 some tests to confirm your diagnosis, including the
- 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.
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 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
- 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.
What Is the Outlook for People with Metachromatic Leukodystrophy?
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
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
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’re a carrier. Genetic counseling may help you to be better
informed about the risks of passing the gene on to your children.