More symptom information
Learn more about specific symptoms of this leukodystrophy in these pages.
Alexander disease is a rare genetic disorder affecting the central nervous system. It is caused by mutations in the Glial Fibrillary Acidic Protein (GFAP) gene, leading to abnormal accumulation of the protein GFAP in astrocytes. Alexander disease is categorised into two types. Type I usually has onset before age 4 and presents with a range of symptoms including failure to grow and gain weight, enlarged head, developmental delays, seizures, muscle stiffness and lack of coordination. Type II usually has onset past the age of 4 and presents with symptoms such as muscle stiffness, lack of coordination, difficulty swallowing and speaking. Treatment mainly focuses on managing symptoms and providing supportive care to enhance the individual’s quality of life.
A new diagnosis can be overwhelming as it brings unique challenges and adjustments, but it is important to remember that you are not alone.
A mutation in the GFAP gene is the cause of Alexander Disease. Normally GFAP is important for supporting the myelin (white matter) that surrounds the nerve fibres in the brain. In Alexander Disease there is an overproduction of abnormal GFAP which results in damage of normal myelin formation and maintenance and impairment of brain function.
In most people with Alexander Disease the mutation in the GFAP gene occurs at the time of conception (this is called de novo) and is not inherited from a parent. However occasionally Type 2 Alexander Disease is caused by a GFAP mutation that has been inherited from one of the parents
This disease is usually sporadic and occurs because of a new mutation, not a mutation inherited from their parents. It typically is not genetically inherited but there are some autosomal dominant cases.
Autosomal dominant: In autosomal dominant conditions, only one copy of the genetic mutation is needed to cause the condition. We all have two copies of every gene, one from our mother and one from our father. Someone with an autosomal dominant condition has one parent with a copy of the genetic mutation and the condition themselves. Therefore, someone with an autosomal dominant condition has a genetic mutation on one copy of the gene from their parent with the condition. Each child of a parent with the genetic mutation will have a 50% chance of having the condition and a 50% chance of not having the condition.
Genetic counselling is essential for affected families due to the inheritance pattern of the condition. This is available at hospitals and Regional Genetic Centres. Please contact your doctor if you have any questions.
Learn more about genetic testing and counselling here.
Type 1 Alexander Disease is the most common form and presents in the first 2 years of life.
Rarely it may present in the neonatal period. Symptoms typically include encephalopathy (brain disease, damage or malfunction), an enlarged brain and head, seizures, failure to thrive, stiffness in the arms and legs, delayed learning and physical development. Affected individuals have a very reduced life span ranging from several months to several years.
Type 2 Alexander Disease usually presents between the age of 4 and 10 years but may present in the teens or adulthood. Symptoms include: speech difficulties and swallowing abnormalities, spasms of the soft palate (palatal myoclonus), poor coordination and walking difficulties. Other problems include sleep disorders and urinary difficulties.
Progression is slow but eventually leads to respiratory failure. Those with Alexander Disease type 2 may survive for around 25 years post-diagnosis or longer in the adult form.
Learn more about specific symptoms of this leukodystrophy in these pages.
Although there is currently no specific treatment for this leukodystrophy, there is condition management information that may be useful for you in managing your or your loved one’s leukodystrophy.
There may be a current clinical trial, natural history study or patient registry for your condition. Check our current research page and ask your specialist doctor for more information.
We understand that research is a significant priority and source of hope for the leukodystrophy community. There is more research in leukodystrophy now than ever before. Alex TLC actively promotes and supports research in a number of ways.
Every month we update our database of research summaries with the most recent research. This includes summaries of leukodystrophy articles, clinical trials and pharmaceutical press releases. Our summaries allow our community to read about relevant recent research developments in a format that is easily understood.
Learn about the ways in which we can help in the how we support you section. When you or a family member are diagnosed with a leukodystrophy it may be difficult to know where to go for more advice – this information could help.
Our services and equipment section is here to help leukodystrophy patients and their families manage their condition. All information is based on our knowledge of UK services, however, our team are happy to receive support requests from other countries – email us.
You may be introduced to many different medical professionals which you may find confusing. View our guide to the health and care professionals you may encounter, with short descriptions about what they do.
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