Leukodystrophy

What is leukodystrophy?

Leukodystrophies are a group of rare neurological disorders in which the protective coating around the nerves in your brain or spine (also called myelin or “white matter”) is broken down. Without myelin, nerves can’t communicate well. Leukodystrophies cause ongoing damage to myelin, which leads to a progressive (gradual) loss of neurological function. Your brain and the rest of your body can’t receive signals from each other.

Symptoms are different for different types of leukodystrophy, but may include problems with speaking, walking, vision, hearing, thinking and other neurological functions. Not everyone will have all the symptoms. These diseases are often fatal, but new therapies and clinical trials have shown promise in managing them.

How common is this condition?

Each type of leukodystrophy is rare. In the U.S. and Canada, the conditions all together affect anywhere from 1 in 6,000 to 1 in 100,000 live births. In Asian countries, the diseases occur in 3 out of every 100,000 live births.

What are the symptoms of leukodystrophy?

Leukodystrophy symptoms vary widely across the different disease types. But most forms of the disease result in gradual loss of neurological function, which can cause a variety of symptoms. Leukodystrophies can cause problems with:

• Balance
• Strength
• Cognition (learning, thinking and remembering)
• Eating and swallowing
• Hearing
• Movement and coordination
• Speech
• Vision

Leukodystrophy types

Researchers have identified more than 50 types of leukodystrophy. They’re still discovering new forms. Each form of leukodystrophy is the result of a different genetic mutation (change in your DNA) and causes different symptoms. The age of onset (age at which symptoms start) for leukodystrophy varies based on type. Some leukodystrophy types include:

• Adrenoleukodystrophy (ALD): ALD affects both the white matter in your brain and spinal cord and your adrenal glands, which control hormone production. Symptoms start in childhood or early adulthood. They may include difficulties with learning, changes in vision or hearing, imbalance and lack of coordination, fatigue and/or weight loss.
• Adult-onset autosomal-dominant leukodystrophy (ADLD): ADLD appears around age 40 or 50. ADLD causes problems with strength, movement and cognition (thinking and remembering). It also affects involuntary (automatic) body functions like blood pressure and heart rate.
• Alexander disease: Alexander disease causes developmental delays, seizures and difficulty with walking. It typically develops in newborns or children, but there are types of Alexander disease that can first show symptoms in adulthood.
• Canavan disease: Canavan disease causes developmental delay, weakness, difficulty with swallowing, seizures, irritability and/or vision changes. Symptoms usually appear in early infancy, but there are forms of this disease that can cause symptoms later in life.
• Cerebrotendinous xanthomatosis (CTX): CTX affects your white matter tendons (tissue that attaches muscle to bone) and heart. Symptoms can include changes in thinking, difficulty walking, abnormal movements, seizures or hallucinations. Symptoms appear in childhood and progress through adulthood.
• Childhood ataxia with central nervous system hypomyelination (CACH): CACH is also called vanishing white matter (VWM) disease due to its destruction of the white matter in your brain and spinal cord. CACH causes vision loss due to optic atrophy (deterioration of the main nerve in your eye) and speech loss in the first five years of life. It can also lead to seizures, difficulty with walking and balance, and spasticity (abnormal muscle tightness).
• Krabbe disease: Krabbe disease is also called globoid cell leukodystrophy. Symptoms often appear in infancy and can cause weakness, difficulty with feeding, irritability, developmental delay, neuropathy (damage to your peripheral nerves, which can cause numbness, tingling and weakness) and seizures. Symptoms can occur at a later age as well.
• Metachromatic leukodystrophy: Metachromatic leukodystrophy can appear in babies, children or adults. Symptoms include changes in thinking, changes in behavior, changes in vision or hearing, seizures, neuropathy, dementia and blindness.
• Pelizaeus-Merzbacher disease (PMD): Symptoms of PMD include weakness, abnormal eye movements, spasticity and developmental delay, which progress over time. PMD mainly affects people assigned male at birth (AMAB).
• Refsum disease: Refsum disease can start at any age, from infancy to adulthood. Symptoms include loss of vision, imbalance, difficulty walking and numbness/tingling in your hands and feet. It can also cause dry skin, heart rhythm abnormalities or problems with your liver, kidney or bones.

What causes leukodystrophy?

Leukodystrophy is the result of gene mutations (changes to your DNA) in the genes that control the growth or function of myelin. Myelin, also called “white matter,” is the protective coating around the nerves in your brain and spine. Without this protective covering, nerve cells can’t function correctly.

Gene mutations may be passed down from parents to their biological children, but these mutations may also happen randomly as cells grow and divide.

You can have a mutated leukodystrophy gene without developing the disease. This means you’re a carrier. Carriers can still pass the mutated genes on to their children. If you’re a carrier of a gene mutation that causes leukodystrophy, you may want to consider genetic counseling. A genetic counselor reviews your biological family history and helps you determine your risk of passing a mutated gene to your children.

What are the risk factors for this condition?

There are no preventable risk factors for leukodystrophy. Some ethnicities have a higher risk for certain leukodystrophies. Most leukodystrophies affect people assigned male at birth (AMAB) and people assigned female at birth (AFAB) equally. But some, like Pelizaeus-Merzbacher disease, mostly appear in people AMAB.

How is leukodystrophy diagnosed?

Your healthcare provider will evaluate your symptoms and review your personal and biological family health history. They’ll also perform a physical exam and a neurological exam.

Other tests may include:

• Newborn screening exams
• Blood and saliva tests (genetic testing) to check for mutated genes in your DNA
• Imaging exams, like an MRI scan, to check the white matter in your brain and spinal cord

Even with testing, leukodystrophy is difficult to diagnose due to the wide-ranging symptoms. Many leukodystrophies go undiagnosed.

How is leukodystrophy treated?

There’s no cure for leukodystrophy. Many symptoms can be treated to help you feel better and preserve some neurological function. These treatments may include:

• Medication for seizures, muscle tightness and movement problems
• Nutritional therapy or feeding tubes for eating and swallowing issues
• Hormone therapy for adrenal gland dysfunction
• Physical, occupational and speech therapy for mobility, balance, speaking and other skills

Gene therapy is a treatment available for some forms of leukodystrophy. The technique delivers genetic material to your cells and changes how your cells produce certain proteins.

A stem cell or bone marrow transplant may improve some types of leukodystrophy, but this treatment is only helpful in rare cases. Chenodeoxycholic acid (CDCA) replacement therapy can treat CTX if it’s diagnosed early.

Several clinical trials are also underway for the treatment of some forms of leukodystrophy. Talk to your healthcare provider to see if this is an option for you or your child.

What is the life expectancy of leukodystrophy?

Leukodystrophies are progressive, so the neurological problems get worse over time. Many children with leukodystrophy die before their teenage years. Some people survive into adulthood. While these diseases are often fatal, new treatment approaches and clinical trials have offered hope for people with the condition.