Alexander Disease is a form of Leukodystrophy that is a fatal, neurodegenerative disease. This means that the neurons in the brain continually lose structure and functionality over time.
Typically, those affected by this disorder appear healthy until the onset of symptoms. Onset of the disease is due to the destruction of myelin in the brain caused by mutations in the GFAP (Glial Fibrillary Acidic Protein) gene. This essential protein is responsible for providing strength to important cells.
Myelin is the fatty/protein substance that covers the nerve fibers in the brain. Myelin acts as an insulator to promote the rapid transmission (communication) of nerve impulses. When myelin is damaged, there is disruption in this transmission of nerve impulses. The end result is severely impaired functioning of the nervous system.
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| Alexander Disease |
Alexander Disease is progressive and individuals with the disease will slowly lose their ability to function normally. This means simple abilities like eating and walking are slowly lost over time.
This disorder is also the only Leukodystrophy that has the presentation of Rosenthal Fibers. Rosenthal fibers are considered abnormal protein deposits that impair cell function. In Alexander Disease, Rosenthal fibers are found in the cells that support other cells in the brain and ultimately play a part in the abnormality of myelin.
Is Alexander Disease referred to as any other names?
Yes. While Alexander’s Disease is the most prevalent and widely used name, there are multiple other names that can reference Alexander’s Disease as follows:
- Abbreviations: ALX and AxD
- Alexander’s Disease Leukodystrophy
- Demyelinogenic Leukodystrophy
- Fibrinoid Leukodystrophy
- Dysmyelinogenic Leukodystrophy with Megalobarencephaly (Megalobare)
- Leukodystrophy with Rosenthal Fibers
- Fibrinoid Degeneration of Astrocytes.
- Hyine Panneuropathy
- Megalencephaly with Hyaline Inclusion
- Megalencephaly with Hyaline Panneuropathy
- White Matter Disease
Alexander’s Disease was actually named after Australian pathologist, Dr. W. Stewart Alexander. Dr. Alexander was the first Doctor to describe an infantile case of Alexander’s Disease in 1949.
How does Alexander’s Disease affect the individual?
Over time, individuals with this disorder slowly lose their ability to function due to the loss of previously attained milestones. During this process, there are many symptoms that present throughout the body. These symptoms include but are not limited to:
- Acute Respiratory Failure
- Ataxia: Poor coordination
- Breathing Problems
- Constipation: Inability to have normal bowel movements which can lead to other serious issues
- Developmental Delay
- Difficulty Swallowing
- Failure to Thrive: Insufficient weight gain or loss
- Feeding Issues
- Frequent Vomiting
- Gait Issues: Problems with walking
- Gradual Intellectual Decline
- Hydrocephalus: Cerebrospinal fluid on the brain
- Megalencephaly: Enlarged head and brain. The head size becomes increasingly large and the forehead appears prominent.
- Quadriparesis: Paralysis of arms and legs
- Seizures
- Spasticity: stiffness of the arms and legs.
- Speech Problems
- Symptoms that mimic multiple sclerosis: (Adult Onset)
How do you get Alexander Disease?
Unlike other Leukodystrophies, Alexander Disease is not always hereditary. This disorder can be caused by a sporadic gene mutation within the GFAP gene, meaning the mutation occurs without being inherited from the parents. There are some cases of Adult onset Alexander Disease where the disease has been found to be genetically inherited, however, this is rare.
Could other children in the family also have Alexander Disease?
It is unlikely for siblings of children with Alexander Disease to also have the disease. In most cases, the genetic mutation causing this disorder is spontaneous, meaning that it is not a mutation passed on from either parent. Therefore, it is unlikely that other children from the same parents would have Alexander Disease.
It is important to speak with a geneticist or Alexander Disease expert to discuss the likelihood of the disease being passed down genetically to other members of your family.
How is Alexander Disease diagnosed?
While there are symptoms and clinical studies that can point to Alexander Disease, diagnosis can only be verified through genetic testing. Individuals experiencing symptoms are referred to a genetic and metabolic specialist who can ensure a correct diagnosis is made.
What are the different forms of Alexander Disease?
No matter what form of Alexander Disease an individual is diagnosed with, comprehensive medical care is of timely importance. The Leukodystrophy Care Network (LCN) was established to provide individuals affected by Leukodystrophy with the best quality of care at specialized centers across the country.
For more information and to find a Leukodystrophy Care Center nearest you, please visit the Leukodystrophy Care Network page.
Neonatal
This is a very rare form of this disorder that can occur in the first month of life.
Infantile Onset
The onset of symptoms for the infantile form of Alexander Disease can start anywhere between birth to 4 years of age. Most diagnoses for infantile onset are made within the first 2 years of life. The average age of onset is approximately 6 months. About 80% of diagnoses are infantile onset.
Juvenile Onset
The juvenile form of Alexander Disease usually presents between age 4 and into the early teen years. The most common time frame of diagnosis for this onset is between the age of 4 and 10 years of age. Approximately 14% of Alexander’s Disease diagnosis are juvenile onset.
Adult Onset
The adult form of Alexander Disease is the least prevalent onset and progresses the slowest. Approximately 6% of cases represent this form. Due to the nature of the presentation of Rosenthal fibers in Alexander Disease, some adult onset cases are only discovered by chance during autopsy.
Is there treatment for Alexander Disease?
Unfortunately, there is currently no cure for Alexander Disease, but symptoms are manageable.
With proactive, comprehensive medical care, affected individuals can avoid unnecessary suffering and complications to have the best quality of life possible. For more information, visit the Leukodystrophy Care Network page.
What research is being done to find better treatments & a cure for Alexander Disease?
Hunter’s Hope is committed to funding research for better treatments and a cure for Leukodystrophies. To learn more about the groundbreaking research currently underway, visit the Research section of our website.
There is also current research being done at the University of Wisconsin-Madison, Waisman Center. This research is aimed at understanding the means by which the mutations cause disease, and identifying other genetic factors that influence severity. In addition, they are testing drugs that reduce GFAP accumulation as potential therapeutics and are attempting to identify biomarkers in blood or CSF that would permit monitoring of severity or progression. You can find out more by visiting the University of Wisconsin – Waisman Center page.
Lastly, a research study at the Children’s Hospital of Philadelphia is underway to define the natural history of this disorder. Investigators are obtaining clinical outcome assessments to measure how Alexander Disease affects a patient’s gross motor, fine motor, speech and language function, swallowing and quality of life. The data obtained from this study will be used for the design of future treatment trials. Find out more by visiting the Children’s Hospital of Philadelphia page.
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