Leukodystrophies are a group of rare neurological (nervous system) diseases. They affect the white matter in the brain and spinal cord. White matter is tissue made of insulated nerve fibers.
Leukodystrophies target myelin, which is the protective insulation covering nerve cells. Without myelin, nerves can’t communicate well. Leukodystrophies lead to a progressive loss of neurological function. The brain and the body can’t receive signals from each other. These diseases are often fatal.
What causes leukodystrophy?
Leukodystrophy is the result of changes (mutations) to genes. These genes control the growth or function of myelin. Without this protective covering, nerve cells don’t work correctly.
Most leukodystrophies come from parents passing the genes to their children (inherited). But sometimes gene mutations happen suddenly 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.
What are the symptoms of leukodystrophy?
The symptoms of leukodystrophy vary widely across the different disease types. But most forms of the disease result in gradual loss of neurological function. This means the body and brain have trouble talking to each other. Leukodystrophies can cause problems with:
Balance.
Breathing.
Cognition (learning, thinking, remembering).
Eating and swallowing.
Hearing.
Movement, balance and coordination.
Speech.
Vision.
What are some symptoms of the different types of leukodystrophy?
Each type of leukodystrophy causes different symptoms. Some include:
Adrenoleukodystrophy (ALD) is the most common leukodystrophy. It affects white matter and the adrenal gland, which controls hormone production. Symptoms start in childhood or early adulthood. They range from seizures to paralysis (loss of muscle function).
Adult-onset autosomal dominant leukodystrophy (ADLD) appears around age 40 or 50. It prevents brain cell development and myelin production. ADLD causes problems with movement and cognition (thinking and remembering). It also affects involuntary (automatic) body functions like blood pressure and heart rate.
Alexander disease causes clumps of protein to form in brain cells. It develops in newborns or children. The disease leads to developmental delays and loss of motor skills (muscle movement).
Canavan disease causes spongy, fluid-filled spaces to form in the brain. It prevents the brain from metabolizing (breaking down) brain chemicals and forming myelin. Symptoms usually appear in early infancy.
Cerebrotendinous xanthomatosis (CTX) causes abnormal storage of fats throughout the body. It affects the white matter, tendons (tissue that attaches muscle to bone) and heart. Symptoms appear in childhood and progress through adulthood.
Childhood ataxia with central nervous system hypomyelination (CACH) disrupts myelin formation. It’s also called vanishing white matter (VWM) disease. CACH causes optic atrophy (deterioration of the main nerve in the eye) and speech loss in the first 5 years of life. It also leads to seizures, ataxia (balance and movement problems) and spasticity (abnormal muscle tightness).
Krabbe disease is also called globoid cell leukodystrophy. It causes fatty acids build up and destroy myelin. The disease can cause seizures, delays in development and peripheral neuropathy. Symptoms usually appear in early infancy.
Metachromatic leukodystrophy causes lipids (fats) to build up in white matter and nerves, becoming toxic. It can appear in babies, children or adults. Complications include seizures, dementia and blindness.
Pelizaeus-Merzbacher disease (PMD) causes problems with myelin production. It mainly affects males. The disease can lead to problems with muscle movement, balance and mental function.
Refsum disease causes a fatty acid to build up in cells and harm myelin. Adult Refsum disease (ARD) leads to problems with the brain, eyes, liver, kidneys and bones. Infantile Refsum disease affects muscle movement.
How is leukodystrophy treated?
There’s no cure for leukodystrophy. The following treatments may ease symptoms and preserve some neurological function:
Medication for seizures, muscle tightness and movement problems.
Nutritional therapy or feeding tubes for eating and swallowing problems.
Hormone therapy for adrenal gland dysfunction.
Physical, occupational and speech therapy for mobility, balance, speaking and other skills.
A stem cell or bone marrow transplant may improve some types of leukodystrophy. Chenodeoxycholic acid (CDCA) replacement therapy can treat CTX if it’s diagnosed early. CTX is currently the only treatable form of leukodystrophy.
How is leukodystrophy diagnosed?
Your healthcare provider:
Evaluates your symptoms.
Performs physical and neurological exams.
Reviews your personal and family health history.
Other tests may include:
Blood and saliva tests to check for mutated genes in your DNA.
Imaging exams, such as an MRI or CT 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.