Leukodystrophy

Leukodystrophy disease is a rare, neurological disorder. It affects the function of your central nervous system, which includes your brain and spinal cord. When your nervous system can’t communicate with other parts of your body, your cognitive and physical functions are impacted.

Leukodystrophy is a genetic disorder that primarily affects infants and children. It’s commonly passed on from parent to child, but some types develop suddenly in adults.

Researchers have discovered more than 40 types of leukodystrophies. Symptoms of leukodystrophies get worse over time, and sometimes the disease doesn’t progress until adulthood. There is no cure, but early detection can help slow the disease and improve symptoms.

What is leukodystrophy?

It helps to first understand your central nervous system. Your brain and spinal cord controls how your body functions, including how you move, think, eat, see and hear. Nerve fibers (axons) connect your nerve cells, which send these important messages from your brain and spine.

Nerve fibers are protected by myelin, a sheath-like insulating layer. Myelin-covered nerve fibers make up the white matter in your central nervous system.

When myelin is damaged by a disease, the signals from your nerve cells slow down or stop. This causes a range of neurological symptoms that progressively get worse.

Leukodystrophy is a type of demyelinating disease. All types of leukodystrophy affect your myelin within your white matter and central nervous system differently.

Types & symptoms of leukodystrophy

Leukodystrophy symptoms may be present at birth. They can also develop in childhood or adulthood. Early signs of leukodystrophy in children could be developmental delays or behavior problems.

Different types of leukodystrophy cause varying symptoms. Common symptoms include neurological issues like ataxia (balance and movement problems), spasticity (abnormal muscle tightness) and paralysis (loss of muscle function).

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. Adrenoleukodystrophy (ALD) is the most common type.
• Alexander disease: Causes clumps of protein to form in brain cells. Symptoms include developmental 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, ataxia 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 types of leukodystrophies only affect adults. 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.

End stage leukodystrophy, when the disease is widespread and advanced, includes life-threatening symptoms from significant neurological impairment.

Leukodystrophy risk factors

Leukodystrophies are caused by an abnormal (mutated) gene. It’s often an inherited condition but can also happen randomly.

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

You can carry the mutated leukodystrophy gene and never develop symptoms. If you’re a carrier of the gene, you can't prevent passing it down to your children. Genetic testing can tell you if you’re a carrier of the gene.

Diagnosing leukodystrophy

The first steps in diagnosing a type of leukodystrophy include a review of your medical and family health history. A physical and neurological examination is also needed.

Leukodystrophy diseases can be difficult to diagnose since they cause a range of symptoms that can be related to other conditions.

Tests to diagnose a type of leukodystrophy and rule out other conditions include:

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

Leukodystrophy treatment

Since there is no way to reverse neurological damage, treatment will focus on delaying leukodystrophy disease progression and managing symptoms.

Treatments might include a combination of:

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