Leukodystrophy

Leukodystrophies are a group of progressive neurological diseases. The disorder affects the white matter within your central nervous system (brain and spinal cord). Your central nervous system controls how your body functions, including how you think, hear and move.

Each type of leukodystrophy disease is rare, and it mostly affects infants and children. The disease is caused by an abnormal (mutated) gene and leads to the loss of neurological function. Symptoms usually get worse over time. Sometimes symptoms don’t appear until children grow into adults.

There is no cure for leukodystrophy, but early detection can help manage symptoms and delay the disease’s progression.

Types & symptoms of leukodystrophy

Researchers have identified over 40 different types of leukodystrophy so far. Adrenoleukodystrophy (ALD) is the most common form of the disease.

All forms of leukodystrophy affect your central nervous system, but they may cause different symptoms that include paralysis (loss of muscle function), ataxia (balance and movement problems) or spasticity (abnormal muscle tightness).

Symptoms may be present at birth or develop during childhood or early adulthood. Early signs of leukodystrophy in children could be developmental delays or behavior problems. End stage leukodystrophy, when the disease is advanced, includes life-threatening symptoms.

Types of leukodystrophy disease and their symptoms include:

• Adrenoleukodystrophy (ALD): Causes the buildup of fatty acid chains (VLCFAs) in the brain and adrenal gland, creating inflammation that damages myelin. Symptoms include paralysis, learning disabilities and seizures.
• Alexander disease: Causes clumps of protein to form in brain cells. Symptoms include cognitive delays and loss of muscle movement.
• Canavan disease: Causes your white matter to break down as your brain degenerates into spongy tissue with fluid-filled spaces. Symptoms include an abnormally sized head, weak muscle tone and blindness.
• Childhood ataxia with central nervous system hypomyelination (CACH): Causes the disruption of myelin formation. It’s also known as vanishing white matter disease (VWM). Early symptoms include optic atrophy (damage to the optic nerve) and speech loss. Later symptoms include seizures, balance problems or spasticity.
• Infantile refsum disease: Fatty acids build up in nerve cells, harming myelin. Symptoms appear in early infancy and include trouble with muscle movement and developmental delays.
• Krabbe disease: Causes excessive amounts of fatty acids that destroy myelin. It’s also known as globoid cell leukodystrophy. Symptoms usually appear in infants and include seizures and developmental delays.
• Metachromatic leukodystrophy: Causes the buildup of lipids (fats) in nerve cells that become toxic and damage your myelin. Symptoms include blindness, dementia and seizures.

Some leukodystrophies affect adults only. These include:

• Adult-onset autosomal dominant leukodystrophy (ADLD): This disease appears in adults around age 40 or older and prevents myelin production. Symptoms include blood pressure and heart rate issues, and cognitive problems.
• Adult refsum disease: Excessive fatty acids harm myelin, leading to symptoms like vision loss, deafness or polyneuropathy (pins-and-needles feeling) in the arms, hands, legs or feet.

Risk factors for leukodystrophies

Most types of leukodystrophy are caused by inherited genetic mutations (passed down by one or both parents to a child). It’s possible to be a carrier of the mutated leukodystrophy gene and to never develop symptoms. Other types happen from sudden, sporadic genetic mutations for unknown reasons.

Some ethnicities have a higher risk of leukodystrophy. Most types of the disorder affect men and women equally, but some types affect only men.

If you’re a carrier of the leukodystrophy gene, there’s no way to prevent passing it down to your children. You can learn if you’re a carrier of the gene through genetic testing.

Diagnosing leukodystrophy

Leukodystrophies can be hard to diagnose since they cause a wide range of symptoms that can be related to other conditions.

In both infants and adults, the first steps in diagnosing a type of leukodystrophy include a physical and neurological examination, plus a review of medical and family health history.

Testing may include:

• Blood tests to look for mutated genes.
• MRI or CT scan to check the white matter in the central nervous system.
• Electromyography (EMG) to evaluate how well nerves and muscles are functioning.
• Spinal tap (lumbar puncture) to gather cerebrospinal fluid (CSF) for testing.

Leukodystrophy treatment

With no cure, treatment focuses on delaying leukodystrophy disease progression and managing symptoms.

Treatment may include:

• Medications to help control seizures and improve muscle problems.
• Gene therapy, which may help target mutated genes to stop the disease progress.
• Physical therapy to regain mobility and improve function.