Alexander disease (AxD) is a neurological condition that affects astrocytes, a type of cell in the central nervous system. Astrocytes are support cells for nerve cells (neurons) and maintain a healthy environment in the brain and spinal cord. In AxD, abnormal protein clumps called Rosenthal fibres build up inside astrocytes throughout the brain and spinal cord, and disrupt their normal function. AxD is a progressive (worsens over time) and life-limiting condition that often results in early death. 

AxD is broadly classified into two types, which is often based on when the condition presents. However these categories are not exclusive, and could be a continuum of symptoms.  

AxD Type 1 is typically characterised by: 

• most often early onset of symptoms (under age 4) 
• very slow growth and weight gain (failure to thrive) 
• physical developmental delays  
• progressive (worsening over time) intellectual disability 
• seizures 
• large head (macrocephaly) 

AxD Type II is typically characterised by:

• most often later onset (4 years of age or older) 
• vomiting 
• difficulty breathing or talking 
• difficulty swallowing  
• poor coordination (ataxia) 
• stiff or jerky muscles and restricted movement (spasticity) 

AxD is also often classified as a type of leukodystrophy because astrocyte dysfunction can lead to problems in the brain’s white matter. In many individuals, the build-up of Rosenthal fibres can lead to a loss of brain white matter, which is the insulating coat (myelin) that surrounds neurons and allows them to communicate quickly with each other. Not all individuals with AxD may have this white matter defect, in particular some individuals with later onset AxD. 

Below on this page is some information about this condition as well as links to useful resources for Australians living with a rare disease. 

Synonyms: AxD, Alexander’s leukodystrophy, fibrinoid leukodystrophy, Alexander’s astrogliopathy, dysmyelogenic leukodystrophy, fibrinoid degeneration of astrocytes, hyaline panneuropathy, leukodystrophy with rosenthal fibers, megalencephaly with hyaline inclusion. 

AxD was historically classified into three different categories based on the age symptoms began: infantile Alexander disease, juvenile Alexander disease, adult Alexander disease. The modern classifications (type I and type II) are based on differences in symptoms and other features that doctors can detect through their examinations, such as a characteristic pattern on an MRI.

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA: 58 Alexander disease 

ORPHA: 363717 Alexander disease type I 

ORPHA: 363722 Alexander disease type II 

ICD-11: 8A44.2 Alexander disease 

Rare diseases typically display a high level of symptom complexity. There is often a wide range of symptoms and the symptoms may vary between individuals in terms of its presentation, severity, duration and impact. 

Please speak to your medical team to learn more about the symptoms of this condition. 

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

Majority of AxD are caused by disease-causing genetic changes (variants) in the glial fibrillary acidic protein (GFAP) gene on chromosome 17. In some cases, the cause is unknown. 

For most individuals with AxD, their genetic variant in GFAP gene occurs randomly (de novo) prior to birth and is not passed down (inherited) from their parents. In rare cases, the autosomal dominant genetic variant was inherited from an affected parent. More information on autosomal dominant inheritance pattern can be found at Centre for Genetics Education: Autosomal dominant inheritance factsheet.

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information about genetic counselling can be found at: 

• Information on Genetic Services 
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed 

A timely diagnosis is critical for better patient outcomes, the provision of the best possible care and treatment options, access to services and support, increased reproductive confidence and the ability to participate in clinical trials. 

Please speak to your medical team to learn more about the available diagnostic pathways for this condition. 

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities.

Healthcare professionals involved in the care of individuals with AxD may include general practitioners (GP), paediatricians, geneticists and neurologists. The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here. 

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

For many rare diseases, palliative care services may be relevant and useful. Palliative care services are available for people (adults, children and their families) living with a life-limiting illness and is not only for end-of-life care. It can also help at any stage of illness from diagnosis onwards, and will look different for different people. Palliative care services provide assistance, support, resources and tools to help people manage their illness and the symptoms, ease pain, and improve comfort and quality of life. If this is relevant to you and you wish to find out more information about palliative care and how it can help you, please visit:

• Australian Institute of Health and Welfare: Palliative care Overview
• Australian Government Department of Health, Disability and Ageing: Palliative care
• Palliative Care Australia

If you know of any relevant care guidelines, please let us know via the Contribute page. 

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

In addition, individuals, their parents, families and carers often develop extensive expertise on their specific rare disease. It is important to recognise that they can contribute valuable knowledge about their rare condition. Rare diseases often impact individuals differently, so it’s important to consider a person’s lived experience.

If you know of any relevant emergency management guidelines or information relevant to emergency care, please let us know via the Contribute page. 

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries. For more information, please visit the RARE Portal’s Considerations for Participating in Health and Medical Research page.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

It is best to discuss your interest in research, including clinical trials,  with your medical team to determine suitability and eligibility.

Australian Organisation:
Leukodystrophy Australia 
Website: https://leuko.org.au/ 
Leukodystrophy Australia is the national peak organisation representing people impacted by leukodystrophy. Leukodystrophy Australia collaborates with local, national and international stakeholders to advance the care of their members, improve quality of life and ultimately seek a cure for leukodystrophy.

International Organisation:
End Alexander Disease (United States of America)
Website: https://www.endaxd.org/

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

Alexander disease varies between individuals, and each person’s experience is unique.  

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

People living with a rare disease often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information on Alexander disease can be found at: 

• Australian Leukodystrophy Clinical and Research Program: Alexander Disease Factsheet 
• Genetic and Rare Diseases (GARD) Information Center: Alexander Disease 
• National Organization for Rare Disorders (NORD): Alexander Disease 

GeneReviews®: Alexander Disease 

Online Mendelian Inheritance in Man, OMIM®: # 03450; Alexander Disease; ALXDRD 

Orphanet: Alexander Disease 

Orphanet: Alexander disease type I 

Orphanet: Alexander disease type II 

Human Phenotype Ontology (HPO): Alexander Disease 

Human Phenotype Ontology (HPO): Alexander Disease type I 

Human Phenotype Ontology (HPO): Alexander Disease type II 

Inborn Errors of Metabolism Knowledgebase (IEMbase): #IEM1662; GFAP-related Alexander disease 

This page has been developed by Rare Voices Australia (RVA)’s RARE Portal team. If you would like to see more information added to this page, please reach out via the Contact form. If you would like to share relevant resources for this condition, please visit the Contribute page. 

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.