Alexander disease (AxD) is a rare condition affecting the central nervous system (CNS). It belongs to a group of disorders known as leukodystrophies, which involve the destruction of myelin, the protective sheath around nerves.

AxD affects the white matter of the CNS — deeper brain tissues that allow different areas of the brain to communicate and exchange information. The condition’s name comes from Dr. W. Stewart Alexander, a physician who first described the condition in 1949.

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AxD is a rare genetic neurological condition. It results from genetic changes that affect nerve fibers. AxD belongs to a group of rare conditions called leukodystrophies. These conditions affect the CNS by damaging white matter.

White matter includes nerve fibers, which connect nerve cells, and myelin, the protective layer that covers nerve cells and helps speed up signals between them.

Damaged white matter cannot function normally, leading to the slowing or blocking of signals between nerve cells. This is why leukodystrophies such as AxD can cause many symptoms relating to movement and thinking.

AxD can appear at any age, but most cases begin in infancy or early childhood. At present, researchers cannot determine the incidence of AxD, but some suggest that it may occur in 1 in 1 million births. Doctors have identified roughly 500 cases since 1949.

Healthcare professionals divide AxD into two clinical forms: type 1 and type 2. AxD type 1 is more common and often presents when a person is less than 4 years old. AxD type 2 usually presents at ages 4–10 years but may occur in adolescence or adulthood. Doctors may also diagnose a neonatal type if symptoms occur soon after birth.

Most cases of AxD are the result of changes in the GFAP gene, which is present on chromosome 17. This gene is responsible for producing a protein called glial fibrillary acidic protein.

At normal levels, this protein supports the myelin sheath. However, the change in this gene causes the protein to build up. Instead of being beneficial to myelin, the extra protein has a toxic effect and damages the myelin.

Healthcare experts refer to this buildup of protein as Rosenthal fibers. The buildup of protein occurs in astrocytes, which make up most of the cells in the CNS, help it function correctly, and support the formation of myelin.

This damage results in the characteristic symptoms of AxD. This is why some healthcare experts may refer to AxD as an astrogliopathy, or a disease of astrocytes.

Typically, people do not inherit the genetic change responsible for AxD. Instead, the change is often sporadic, meaning that it occurs spontaneously.

But in some cases, a person may inherit AxD from a parent in an autosomal dominant pattern. This means a person needs to receive only one copy of the genetic change for AxD to occur.

Symptoms of neonatal AxD may include:

  • seizures
  • fluid buildup in the brain and high protein levels in the cerebrospinal fluid
  • severe motor and intellectual disability

Symptoms of type 1 AxD, or the infantile form of AxD, may include:

  • seizures
  • enlargement of the brain and head
  • stiffness in the limbs
  • delays in intellectual and physical development
  • recurring vomiting and trouble gaining weight

Symptoms of type 2 AxD, or the juvenile and adult form of AxD, can include:

  • speech difficulties
  • trouble swallowing
  • a lack of coordination
  • curving of the spine (scoliosis)
  • recurring vomiting and trouble gaining weight

Typically, a doctor can diagnose AxD based on physical symptoms, imaging tests, and genetic testing. For example, healthcare professionals will use CT or MRI scans to identify cerebral white matter changes and swelling.

If doctors suspect that a person has AxD, it is usually necessary to perform genetic testing, using either a blood or cheek swab, to confirm the diagnosis.

Because a change in the GFAP gene may not be present, a negative result does not rule out AxD. Therefore, it is also important to rule out more common conditions with similar symptoms, such as Leigh syndrome and Tay-Sachs disease.

Currently, there is no known cure for AxD. Treatment aims to manage symptoms and help improve quality of life. For example, surgery to place a shunt may help drain excess fluid that is putting pressure on the brain.

Genetic counseling may be an option for some people. Additionally, if a person is pregnant and already has a child with AxD, doctors may be able to diagnose AxD in the fetus.

Alexander disease is a rare neurological condition that happens when a genetic change results in the buildup of protein, which damages nerve fibers. This leads to symptoms such as seizures, fluid buildup in the brain, and intellectual and physical disability.

A doctor can use imaging studies and genetic testing to diagnose the condition. At present, no cure is available. Treatment aims to manage symptoms and improve quality of life.