Metachromatic Leukodystrophy

What is metachromatic leukodystrophy?

Metachromatic leukodystrophy (MLD) is a rare genetic condition that leads to damage to the white matter of your central nervous system (brain and spinal cord) and peripheral nerves. MLD is one of several lysosomal storage diseases.

White matter damage happens when fatty materials called sulfatides build up in your cells. The buildup impairs the growth of the myelin sheath (the protective covering around nerve fibers). Myelin gives white matter its color.

This damage causes a decline in mental and motor (muscle movement) functions. Symptoms of MLD get worse over time, and usually results in death years after diagnosis.

Metachromatic leukodystrophy gets its name from the way cells with a buildup of sulfatides appear when you look at them under a microscope. The sulfatides appear metachromatic, which means they pick up color differently than the surrounding cellular material when a pathologist stains them for examination. “Leukodystrophy” means progressive destruction of white matter (“leuko” means “white” and “dystrophy” means “wasting away”).

Forms of MLD

Metachromatic leukodystrophy has three distinct forms:

• Late infantile MLD: This form typically affects babies who are between 12 and 20 months old. It causes walking issues, developmental delays, blindness and dementia. Most children with late infantile MLD die by age 5. Late infantile MLD is the most common form of MLD, representing 50% to 60% of cases.
• Juvenile MLD: This form affects children between the ages of 3 and 10. It causes intellectual decline, behavioral difficulties, seizures and dementia. Juvenile MLD typically results in death 10 to 20 years following diagnosis. Around 20% to 30% of people with MLD have this form.
• Adult MLD: This form typically begins after the age of 16. Symptoms include psychiatric changes, seizures and dementia. It usually results in death within six to 14 years after diagnosis. About 15% to 20% of people with MLD have this form.

How rare is metachromatic leukodystrophy?

MLD is rare. Researchers estimate that it affects 1 in every 40,000 people in the United States. MLD may be more common in certain isolated populations. For example, the Navajo have a higher prevalence rate of 1 in every 2,500 people.

What are the signs and symptoms of metachromatic leukodystrophy?

Symptoms of metachromatic leukodystrophy can vary based on the form. In general, all forms lead to a worsening of neurological functions, including muscle movement, intellect, mood, personality and more.

Symptoms of late infantile MLD

Babies with late infantile MLD develop as expected at first. After about the first year of life, they then develop the following symptoms:

• Difficulty walking, which eventually leads to an inability to walk.
• Weak muscle tone (hypotonia).
• Developmental delays.
• Difficulty speaking (dysarthria).
• Progressive loss of vision that leads to blindness.
• Difficulty swallowing (dysphagia).
• Dementia.

Symptoms of juvenile MLD

Signs and symptoms of juvenile MLD include:

• Intellectual decline, which may present as a decline in school performance.
• Behavioral difficulties.
• Personality changes.
• Lack of control over muscle movement.
• Peripheral neuropathy.
• Seizures.
• Dementia.

Symptoms of adult MLD

Adult MLD mainly causes psychiatric changes with minor or no motor (movement) symptoms. The first signs of adult MLD may be alcohol use disorder, substance use disorder and/or difficulties at school or work.

Other symptoms of adult MLD include:

• Psychiatric issues, such as hallucinations, psychosis or schizophrenia.
• Seizures.
• Peripheral neuropathy.
• Dementia.

Healthcare providers often misdiagnose adult MLD as bipolar disorder and/or dementia.

What causes metachromatic leukodystrophy?

The cause of metachromatic leukodystrophy is a gene mutation (change) that you inherit from both of your biological parents.

Most people with MLD have mutations in the ARSA gene, which provides instructions for making the enzyme arylsulfatase A. This enzyme helps break down sulfatides. Due to the mutation, people with MLD don’t make enough arylsulfatase A, which leads to a buildup of sulfatides. Excess sulfatides are toxic to the white matter in your nervous system and damage these cells.

Some people with MLD have mutations in the PSAP gene. This gene also gives instructions for breaking down sulfatides.

Is metachromatic leukodystrophy genetic?

Yes, you inherit MLD in an autosomal recessive pattern. The biological parents of a person with an autosomal recessive condition each carry one copy of the mutated gene, but they typically don’t show signs and symptoms of the condition (the parents are “carriers”).

What are the complications of MLD?

The most common complications of MLD include:

• Neurocognitive decline (dementia).
• Blindness from optic atrophy.
• Malnutrition.
• Aspiration pneumonia.
• Death.

How is metachromatic leukodystrophy diagnosed?

If your or your child’s healthcare provider (often, a neurologist) suspects metachromatic leukodystrophy based on your symptoms, they’ll likely order these tests:

• Genetic testing: This can identify mutations in the ARSA and PSAP genes, which are responsible for MLD.
• Biochemical testing: This testing measures your levels of sulfatides. Tests include sulfatase enzyme activity and urine (pee) sulfatide levels.
• Brain MRI: A brain MRI can confirm the diagnosis of MLD. It can show the presence or absence of myelin, as there’s a typical pattern of myelin loss in people who have MLD.

You or your child will likely have additional testing if you receive an MLD diagnosis to see how the condition has affected your nervous system. These tests may include:

• Neurocognitive testing.
• Neuropsychological testing.
• Nerve conduction tests.

What’s the treatment for metachromatic leukodystrophy?

There’s no cure for metachromatic leukodystrophy. The focus of treatment is to manage your symptoms and enhance your quality of life. In pre or minimally symptomatic children, healthcare providers may recommend stem cell transplants to slow the progression of the disease.

Supportive treatment may include various medications for the following conditions:

• Seizures (anticonvulsant medications).
• Spasticity (muscle relaxants).
• Mood disorders (antidepressants).
• Pain (NSAIDs and other medications).

Other types of therapy may include:

• Physical therapy to help with muscle strength and stiffness.
• Occupational therapy to improve your ability to perform daily tasks.
• Speech therapy to help with any speaking and swallowing issues.
• Psychotherapy to help with mental health conditions.
• Percutaneous endoscopic gastronomy (PEF) to help with feeding issues and nutrition.

You or your child may also wish to receive palliative care. Palliative care provides symptom relief, comfort and support to people living with serious conditions, including MLD. It also provides support to caregivers and those impacted by a loved one’s condition.

Palliative care complements the care you receive from the providers who help you manage MLD. It helps you live more comfortably — with the medical, social and emotional support necessary to cope with a serious health condition.

Can metachromatic leukodystrophy be prevented?

As metachromatic leukodystrophy is a genetic (inherited) condition, there’s nothing you can do to prevent it.

If you have a biological family member with MLD, you may want to consider genetic counseling if you’re thinking of having a biological child to see if you’re a carrier of the genetic mutation.

What is the prognosis for metachromatic leukodystrophy?

The prognosis (outlook) for metachromatic leukodystrophy is poor. It’s a progressive disease, which means the symptoms spread and/or get worse over time. People with MLD eventually lose all muscle and mental functions, which results in death.

What is the life expectancy of metachromatic leukodystrophy?

The life expectancy of metachromatic leukodystrophy depends on the age at which a person is first diagnosed.

• Late infantile form: Death typically happens within five to six years of diagnosis.
• Juvenile form: Progression is slower in this form of the disease. It typically results in death 10 to 20 years following diagnosis.
• Adult form: Death typically happens within six to 14 years after diagnosis.

How do I take care of my child or myself?

If you or your child have metachromatic leukodystrophy (MLD), it’s important to advocate for yourself and them to ensure you and they get the best medical care possible. Advocating for care can help you or your child have the best possible quality of life.

You and your family may also want to consider joining a support group to meet others who can relate to your experiences.

When should I see my healthcare provider?

If you or your child have metachromatic leukodystrophy, you’ll need to see your healthcare team regularly to monitor the progression of the condition and to adjust your treatment plan.

A note from Cleveland Clinic

Understanding your or your child’s metachromatic leukodystrophy (MLD) diagnosis can be overwhelming. Your healthcare team will help you find a symptom management plan that’s unique to your needs. It’s important to make sure you’re getting the support you need and to stay attentive to your health. Know that your healthcare team will be there to support you and your family.