Alexander Disease

What is Alexander disease?

Alexander disease is an extremely rare nervous system (neurological) disorder. It’s a type of leukodystrophy, conditions that affect white matter in your brain.

Alexander disease damages myelin, the fatty white substance that protects nerve fibers in your brain. Myelin helps send nerve impulses from the brain throughout your body.

People with Alexander disease may have developmental delays, seizures and other issues. The disease progressively worsens and can be life-threatening. There isn’t a cure.

How common is Alexander disease?

Alexander disease is extremely rare, occurring in approximately 1 in 1 million births. Australian physician Dr. W. Stewart Alexander first identified the disease in 1949.

What are the types of Alexander disease?

Healthcare providers determine the Alexander disease type based on when symptoms appear. Types of Alexander disease include:

• Neonatal: This rare form develops during the first month of life.
• Infantile: About 80% of Alexander disease diagnoses occur before an infant is 2.
• Juvenile: Symptoms may appear between ages 2 and 13. Symptoms most commonly arise between 4 and 10 years old. Juvenile-onset Alexander disease accounts for about 14% of all diagnoses.
• Adult: This uncommon type has mild symptoms. It can develop any time after the late teen years. It accounts for 6% of all Alexander disease diagnoses.

What causes Alexander disease?

A change (mutation) in a gene that makes glial fibrillary acidic protein (GFAP) causes 95% of Alexander diseases. There isn’t a known cause for the remaining 5%.

Typically, GFAP proteins bind together to form long chains (filaments). The filaments support and strengthen cells in your nervous system.

When you have Alexander disease, abnormal clumps of proteins called Rosenthal fibers settle in cells where they don’t belong. These fibers damage myelin.

Who is at risk for Alexander disease?

Anyone can develop Alexander disease. The gene change occurs for no known reason. In a few cases, a person inherits the gene change from a parent. But most people don’t have a family history of the disease.

What are the symptoms of Alexander disease?

Symptoms of Alexander disease vary depending on the age of onset or disease type.

Neonatal Alexander disease

Symptoms appear within the first month of life. They include:

• Hydrocephalus (buildup of fluid in your child’s brain).
• Megalencephaly (enlarged brain and head).
• Seizures (epilepsy).
• Spasticity.
• Developmental delays.
• Failure to thrive or grow as expected.

Infantile Alexander disease

Signs of infantile Alexander disease typically appear within the first six months but may occur as late as 24 months. Symptoms are similar to the neonatal type.

Juvenile-onset Alexander disease

Signs of juvenile-onset Alexander disease often appear between 4 and 10 years old. Symptoms include:

• Difficulty swallowing and speaking.
• Ataxia (problems with balance, coordination and movements).
• Muscle problems, such as spasticity, muscle pain or muscle spasms.
• Frequent vomiting.

Adult-onset Alexander disease

Signs of adult-onset Alexander disease can show up any time during adulthood. The symptoms are those of juvenile-onset Alexander disease, along with tremors. Parkinson’s disease or multiple sclerosis cause many similar symptoms.

How is Alexander disease diagnosed?

Your healthcare provider will perform a physical exam and assess your or your child’s symptoms. You or your child may also get:

• MRI to check for changes in your brain.
• Genetic test (a type of blood test) to look for the gene change that causes most cases of Alexander disease.

How is Alexander disease managed or treated?

Treatments for Alexander disease focus on relieving symptoms and slowing disease progression. There isn’t a cure, but researchers are working to develop new therapies in clinical trials. You can talk to your healthcare provider to see if a clinical trial is right for you or your child.

Depending on symptoms, treatments may include:

• Anti-seizure medications.
• Physical, occupational and speech therapies.
• Shunt surgery to treat hydrocephalus by draining excess fluid from your brain.

What are the complications of Alexander disease?

Alexander disease symptoms worsen over time. A person with Alexander disease may need:

• Mobility devices like wheelchairs or walkers.
• Tube feedings (enteral nutrition) to get enough nutrients.

How can I prevent Alexander disease?

Experts aren’t sure why some people develop the gene change that causes Alexander disease. In most instances, there isn’t a way to prevent the disease.

If you have a family history of Alexander disease 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 (PGD). This is when you undergo in vitro fertilization (IVF) with healthy embryos that don’t have the GFAP gene change that causes Alexander disease.

What is the prognosis (outlook) for people who have Alexander disease?

The prognosis for people with Alexander disease 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 birthdays.
• 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.

When should I call my healthcare provider?

You should call your healthcare provider if you or your child with Alexander disease experiences:

• Balance or mobility problems.
• Difficulty breathing, swallowing, eating or speaking.
• Nausea and vomiting.
• Seizures.

What questions should I ask my healthcare provider?

You may want to ask your healthcare provider:

• What type of Alexander disease do I (or my child) have?
• What’s the best treatment?
• Should family members get a genetic test for Alexander disease?
• What signs of complications should I look out for?

A note from Cleveland Clinic

Alexander disease is a lifelong condition that gets progressively worse. Rarely, the disease runs in families. Genetic tests can identify the gene change that causes Alexander disease. While there isn’t a cure, treatments can provide symptom relief. Researchers continue to look for better therapies to treat this uncommon disease.