Metachromatic leukodystrophy (MLD) is a genetic condition that causes a progressive decline in your mental and motor (movement) functions. Symptoms get worse over time. Treatment for the condition is mainly supportive and includes therapies like medication, occupational therapy and a feeding tube.
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”).
Metachromatic leukodystrophy has three distinct forms:
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.
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.
Babies with late infantile MLD develop as expected at first. After about the first year of life, they then develop the following symptoms:
Signs and symptoms of juvenile MLD include:
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:
Healthcare providers often misdiagnose adult MLD as bipolar disorder and/or dementia.
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.
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”).
The most common complications of MLD include:
If your or your child’s healthcare provider (often, a neurologist) suspects metachromatic leukodystrophy based on your symptoms, they’ll likely order these tests:
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:
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:
Other types of therapy may include:
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.
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.
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.
The life expectancy of metachromatic leukodystrophy depends on the age at which a person is first diagnosed.
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.
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.
Last reviewed by a Cleveland Clinic medical professional on 02/06/2023.
Learn more about our editorial process.