What is MLD
Understanding the disease
What is metachromatic leukodystrophy?
Metachromatic leukodystrophy (MLD) is a rare genetic disorder that affects many parts of the body, including the brain, the nerves outside of the brain and spinal cord (peripheral nerves), and the gallbladder. It is a type of leukodystrophy, a group of conditions that affect the white matter of the brain. In MLD, fatty substances (called sulfatides) build up and damage the myelin sheath — the protective coating around nerve cells in the brain and spinal cord — which helps messages travel quickly between cells. Without healthy myelin, messages from the brain travel slowly or stop altogether, leading to serious nerve problems.
Causes of metachromatic leukodystrophy
Most people with MLD are born with a change in the ARSA gene. This gene makes a helpful protein that breaks down sulfatides. In people with MLD, the body doesn't make enough of this protein, so sulfatides build up and slowly damage the nerves.
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For a small number of people with MLD, a change in a different gene, called PSAP, causes the same problem. Although the two genes are different, the symptoms and outcome are the same.
Signs and symptoms of metachromatic leukodystrophy
There are multiple forms of MLD, based on when symptoms appear: late infantile, early juvenile, late juvenile and adult.
In children, symptoms include:
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Slow development or delays in reaching milestones
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Trouble walking
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Unusual eye movements
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Problems with feeding
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Constipation
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Nerve damage
In adults, symptoms include:
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Changes in thinking, memory or learning
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Mental health or behavioral changes
Gallbladder disease can affect both children and adults with MLD.
Genetic Testing
Testing and diagnosis for metachromatic leukodystrophy
In addition to looking at physical symptoms, diagnosing MLD involves several tests. Together, results from these tests give a clear picture and help confirm the diagnosis.
A brain MRI (magnetic resonance imaging) can show patterns in brain tissue that are typical of MLD.
​Genetic testing looks for changes in one of the genes linked to MLD. This test is done from a blood or saliva sample or a cheek swab. The results, along with other tests, can lead to a diagnosis of MLD.
Blood and urine tests, called biochemical testing, check levels of arylsulfatases and the concentration of sulfatides.
Neuropsychological testing evaluates how the condition is affecting a person's thinking, memory, problem-solving and focus.
Together, results from these tests give a clear picture and help confirm the diagnosis.
FOLLOW-UP
Patients with MLD need regular monitoring by neurologists, as well as ongoing therapy and coordinated care by other medical subspecialists as needed.
LONG-TERM OUTLOOK
MLD is a progressive, life-limiting disease, with symptoms that worsen over time. However, innovative treatments, like gene therapy, can slow disease progression and improve quality of life.
OUR MISSION
A community built for MLD families
We are a global network of patients, families, advocates and physicians dedicated to helping families impacted by metachromatic leukodystrophy (MLD). We connect you with resources, information, peer support, and the world's leading specialists — wherever you are in your journey.