Alexander Disease (ALX)
What is Alexander disease?
Alexander disease (ALX) is a form of leukodystrophy that is characterized by deposits of abnormal proteins called Rosenthal fibers, along with damage to the myelin sheath.
There are four forms of this disease: neonatal, infantile (onset within the first two years of life), juvenile (onset between ages two and 13), and adult (onset from late teens and on).
What are the symptoms of Alexander disease?
Symptoms typically appear within the first two years of life, as the infantile form of the disease is the most common. They include:
- Stiffness in the limbs
- An enlarged brain and head
- Delayed physical development
- Intellectual disability
For those affected by the juvenile form, symptoms include loss of motor control, issues swallowing, speech difficulties, excessive vomiting, and poor coordination. The adult form, which is the mildest and very rare, tends to mimic the symptoms of multiple sclerosis or Parkinson’s disease.
The neonatal form is the most severe. Infants will experience seizures, severe motor and intellectual disability, and hydrocephalus. Unfortunately, this form is typically fatal within the first two years of life.
What causes Alexander disease?
A mutated GFAP gene is the cause of ALX about 90% of the time, and it is typically a sporadic mutation. This means that parents do not pass it down. If it is inherited, it is in an autosomal dominant pattern. This gene is responsible for GFAP protein, which plays a role in the brain. Medical professionals are unsure as to how this mutation directly leads to the characteristic symptoms.
For the other 10% of those with ALX, there is no identified cause.
How is Alexander disease diagnosed?
An MRI can be used to diagnose the infantile form of the disease, but is less accurate when it comes to the juvenile and adult forms. Even with an MRI, doctors must rule out other conditions, typically other types of leukodystrophies. They can confirm a diagnosis with genetic testing, although not everybody with ALX has a mutated GFAP gene.
What are the treatments for Alexander disease?
There is no cure for this disease, and treatment is symptomatic and supportive. Genetic counseling is recommended for affected individuals and their families.