Metachromatic leukodystrophy is a rare hereditary (genetic) disorder that causes fatty substances (lipids) to build up in cells, particularly in the brain, spinal cord and peripheral nerves. This buildup is caused by a deficiency of an enzyme that helps break down lipids called sulfatides. The brain and nervous system progressively lose function because the substance that covers and protects the nerve cells (myelin) is damaged.

There are three forms of metachromatic leukodystrophy, which involve different age ranges: late infantile form, juvenile form and adult form. Signs and symptoms can vary. The infantile form is the most common and progresses more rapidly than the other forms.

There is no cure for metachromatic leukodystrophy yet. Depending on the form and age of onset, early identification and treatment may help manage some signs and symptoms and delay progression of the disorder.

Damage to the protective myelin covering the nerves results in progressive worsening of brain and nervous system functions, including:

• Loss of the ability to detect sensations, such as touch, pain, heat and sound
• Loss of intellectual, thinking and memory skills
• Loss of motor skills, such as walking, moving, speaking and swallowing
• Stiff, rigid muscles, poor muscle function and paralysis
• Loss of bladder and bowel function
• Gallbladder problems
• Blindness
• Hearing loss
• Seizures
• Emotional and behavioral problems, including unstable emotions and substance misuse

Each form of metachromatic leukodystrophy occurs at a different age and can have different initial signs and symptoms and rates of progression:

• Late infantile form. This is the most common form of metachromatic leukodystrophy, starting around 2 years of age or younger. Progressive loss of speech and muscle function occurs rapidly. Children with this form often do not survive beyond childhood.
• Juvenile form. This is the second most common form and starts in children between 3 and 16 years of age. Early signs are behavior and cognitive problems and increasing difficulty in school. Loss of the ability to walk may occur. Although the juvenile form doesn't progress as fast as the late infantile form, survival is generally less than 20 years after symptoms begin.
• Adult form. This form is less common and typically starts after age 16. Signs progress slowly and may begin with behavior and psychiatric problems, drug and alcohol misuse, and issues with school and work. Psychotic symptoms such as delusions and hallucinations may occur. The course of this form varies, with periods of stable symptoms and periods of rapid decline in functioning. Adults may survive for several decades after initial symptoms.

When to see a doctor

Talk to your doctor if you observe any signs listed above or if you have concerns about your own signs or symptoms.

Metachromatic leukodystrophy is an inherited disorder caused by an abnormal (mutated) gene. The condition is inherited in an autosomal recessive pattern. The abnormal recessive gene is located on one of the nonsex chromosomes (autosomes). To inherit an autosomal recessive disorder, both parents must be carriers, but they do not typically show signs of the condition. The affected child inherits two copies of the abnormal gene — one from each parent.

The most common cause of metachromatic leukodystrophy is a mutation in the ARSA gene. This mutation results in a lack of the enzyme that breaks down lipids called sulfatides that build up in the myelin.

Rarely, metachromatic leukodystrophy is caused by a deficiency in another kind of protein (activator protein) that breaks down sulfatides. This is caused by a mutation in the PSAP gene.

The buildup of sulfatides is toxic, destroying the myelin-producing cells ― also called white matter ― that protect the nerves. This results in damage to the function of nerve cells in the brain, spinal cord and peripheral nerves.

Your doctor will perform a physical examination ― including a neurological exam ― and review symptoms and medical history to check for signs of metachromatic leukodystrophy.

Your doctor may order tests to diagnose the disorder. These tests also help determine how severe the disorder is.

• Lab tests. Blood tests look for an enzyme deficiency that causes metachromatic leukodystrophy. Urine tests can be done to check sulfatide levels.
• Genetic tests. Your doctor may conduct genetic tests for mutations in the gene associated with metachromatic leukodystrophy. He or she may also recommend testing family members, particularly women who are pregnant (prenatal testing), for mutations in the gene.
• Nerve conduction study. This test measures electrical nerve impulses and function in muscles and nerves by passing a small current through electrodes on the skin. Your doctor may use this test to look for nerve damage (peripheral neuropathy), which is common in people with metachromatic leukodystrophy.
• Magnetic resonance imaging (MRI). This test uses powerful magnets and radio waves to produce detailed pictures of the brain. These can identify a characteristic striped pattern (tigroid) of abnormal white matter (leukodystrophy) in the brain.
• Psychological and cognitive tests. Your doctor may assess psychological and thinking (cognitive) abilities and assess behavior. These tests may help determine how the condition affects brain function. Psychiatric and behavioral problems may be the first signs in juvenile and adult forms of metachromatic leukodystrophy.

Metachromatic leukodystrophy can't be cured yet, but clinical trials hold some promise for future treatment. Current treatment is aimed at preventing nerve damage, slowing progression of the disorder, preventing complications and providing supportive care. Early recognition and intervention may improve outcomes for some people with the disorder.

As the disorder progresses, the level of care required to meet daily needs increases. Your health care team will work with you to help manage signs and symptoms and try to improve quality of life. Talk to your doctor about the possibility of participating in a clinical trial.

Metachromatic leukodystrophy can be managed with several treatment approaches:

• Medications. Medications may reduce signs and symptoms, such as behavioral problems, seizures, difficulty with sleeping, gastrointestinal issues, infection and pain.
• Physical, occupational and speech therapy. Physical therapy to promote muscle and joint flexibility and maintain range of motion may be helpful. Occupational and speech therapy can help maintain functioning.
• Nutritional assistance. Working with a nutrition specialist (dietitian) can help provide proper nutrition. Eventually, it may become difficult to swallow food or liquid. This may require assistive feeding devices as the condition progresses.
• Other treatments. Other treatments may be needed as the condition progresses. Examples include a wheelchair, walker or other assistive devices; mechanical ventilation to assist with breathing; treatments to prevent or address complications; and long-term care or hospitalization.

Care for metachromatic leukodystrophy can be complex and change over time. Regular follow-up appointments with a team of medical professionals experienced in managing this disorder may help prevent certain complications and link you with appropriate support at home, school or work.

Potential future treatments

Potential treatments for metachromatic leukodystrophy that are being studied include:

• Gene therapy and other types of cell therapy that introduce healthy genes to replace diseased ones
• Enzyme replacement or enhancement therapy to decrease buildup of fatty substances
• Substrate reduction therapy, which reduces the production of fatty substances

Caring for a child or family member with a chronic and progressively worsening disorder such as metachromatic leukodystrophy can be stressful and exhausting. The level of daily physical care increases as the disease progresses. You may not know what to expect, and you may worry about your ability to provide the care needed.

Consider these steps to prepare yourself:

• Learn about the disorder. Learn as much as you can about metachromatic leukodystrophy. Then you can make the best choices and be an advocate for yourself or your child.
• Find a team of trusted professionals. You'll need to make important decisions about care. Medical centers with specialty teams can offer you information about the disorder, coordinate your care among specialists, help you evaluate options and provide treatment.
• Seek out other families. Talking to people who are dealing with similar challenges can provide you with information and emotional support. Ask your doctor about support groups in your community. If a group isn't for you, maybe your doctor can put you in touch with a family who has dealt with the disorder. Or you may be able to find group or individual support online.
• Consider support for caregivers. Ask for or accept help in caring for your loved one when needed. Options for additional support can include asking about sources of respite care, asking for support from family and friends, and taking time for your own interests and activities. Counseling with a mental health professional may help with adjustment and coping.