Alexander Disease

Alexander disease is an extremely rare neurological disorder and a type of leukodystrophy. This means it affects your brain’s white matter. White matter is a network of nerve fibers in your brain that helps nerve cells communicate.

This disease damages myelin. Myelin is a fatty substance that protects nerve fibers in white matter. It conducts signals throughout your body (signals are how your nerve and brain cells talk to each other). Without healthy myelin, communication breaks down. It can cause developmental delays, seizures and other serious symptoms.

This condition worsens over time and can be life-threatening for certain age groups.

Types of Alexander disease

Healthcare providers determine the type based on when symptoms show up. These include:

• Neonatal: It develops during the first month of life.
• Infantile: It affects children before age 2. This is the most common type.
• Juvenile: Symptoms may appear between ages 2 and 13, but they’re most common between ages 4 and 10.
• Adult: It can develop any time during adulthood, starting after the late teen years.

Symptoms of Alexander disease

Symptoms vary depending on the age they start. Alexander disease is a progressive condition. That means symptoms tend to get worse over time. Your provider can help you manage symptoms to slow their progression.

Neonatal and infantile Alexander disease symptoms

Symptoms of neonatal and infantile types include:

• Developmental delays (like walking or speech delays)
• Growth faltering
• Hydrocephalus (buildup of fluid in your child’s brain)
• Megalencephaly (enlarged brain)
• Seizures
• Spasms, stiff muscles or involuntary muscle movements (spasticity)

Juvenile-onset Alexander disease symptoms

Symptoms of the juvenile type include:

• Difficulty swallowing and speaking
• Frequent vomiting
• Front-to-back and side-to-side spine curvature (kyphoscoliosis)
• Muscle problems (like weakness, pain or spasms, often in the legs)
• Slowed mental functioning (not all cases affect this)

Adult-onset Alexander disease

The symptoms of adult-onset may include those from juvenile onset, along with:

• Tremors
• Sleep disturbances
• Problems with balance, coordination and movements (ataxia)

Symptoms are usually mild for this type.

Alexander disease causes

A genetic variation in the glial fibrillary acidic protein (GFAP) gene causes this condition. Normally, this gene produces proteins that link together to form filaments. These help support and strengthen cells in your nervous system.

With this condition, abnormal clumps of proteins called Rosenthal fibers build up in cells where they don’t belong. These fibers damage myelin, the protective coating around nerve fibers. Myelin is essential for sending signals throughout your body. When a signal disruption happens, nerve communication stops working effectively, leading to symptoms.

Risk factors of Alexander disease

Anyone can develop this disease. And it usually happens randomly. A new genetic variant most often causes it. This happens without any history of the condition in your biological family history.

In rare cases, you may inherit it from your biological family. It passes in an autosomal dominant pattern. This means that you only need one copy of the genetic variant to develop symptoms.

If you have a family history of this condition or another type of leukodystrophy, a genetic counselor can help you understand the risk of passing on the condition to future children. You may consider preimplantation genetic diagnosis. This is when you undergo in vitro fertilization with embryos that don’t have the GFAP gene that causes it.

Complications of Alexander disease

Complications may include:

• Feeding challenges
• Gastrointestinal issues (like acid reflux)
• Mobility issues (difficulty walking independently)
• Obstructive hydrocephalus (the flow of fluid to your brain is blocked)
• Urinary retention

How doctors diagnose Alexander disease

A healthcare provider will perform physical and neurological exams to learn more about your symptoms. An imaging test (MRI) confirms a diagnosis. Your provider is looking for changes to the white matter in your brain on this noninvasive test. They may also recommend a genetic blood test to look for a genetic variant that causes the condition.

How is Alexander disease treated?

Treatments focus on relieving symptoms and slowing disease progression. Your provider may recommend:

• Participating in physical therapy or taking medication like baclofen for spasticity
• Taking antiseizure medications to manage seizures
• Taking proton pump inhibitors to prevent complications from vomiting
• Undergoing surgery to get a shunt to treat hydrocephalus
• Using a feeding tube to get enough nutrients
• Using mobility devices to help you move independently

Your provider may offer other types of treatments to manage complications if they arise.

Researchers are working to develop new therapies in clinical trials. You can talk to your provider to see if a clinical trial can offer benefits for you.

When should I see my healthcare provider?

You should call your healthcare provider if you notice:

• Balance or mobility problems
• Difficulty swallowing, eating or speaking
• Nausea and vomiting (that isn’t related to an illness)
• Seizures

Contact emergency services if you have a seizure for the first time or have trouble breathing.

What is the life expectancy of someone with Alexander disease?

The prognosis varies. The disease is progressive, and children usually develop more severe symptoms as time goes by. Symptoms and lifespan depend on the type:

• Newborns with neonatal Alexander disease are severely disabled. Most pass away before their second birthday.
• Children with the infantile type may live five to 10 years.
• Children with the juvenile-onset disease may live into their 30s or 40s.
• Some adults with Alexander disease have mild or nonexistent symptoms. For many, the disease doesn’t shorten life expectancy.

Talk to your provider for the most up-to-date information about what you can expect. Your case is as unique as you are. It may or may not relate to these statistics.

Care is available for you and your family if your provider suspects a short life expectancy. Mental health professionals are available to help you cope and grieve in your time of need.