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Disease Profile

Alexander disease

Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.


US Estimated

Europe Estimated

Age of onset

All ages





Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.


Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.


dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.


Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other names (AKA)

Alexanders leukodystrophy; Megalencephaly in infancy accompanied by progressive spasticity and dementia


Congenital and Genetic Diseases; Eye diseases; Nervous System Diseases


Alexander disease is a type of leukodystrophy characterized by the destruction of the myelin sheath (the fatty covering that acts as an insulator around nerve fiber) and abnormal protein deposits known as Rosenthal fibers. Most cases of Alexander disease begin before age 2 years (the infantile form). Symptoms of the infantile form include an enlarged brain and head, seizures, stiffness in the arms and/or legs, intellectual disability, and delayed physical development. Less frequently, onset occurs later in childhood (the juvenile form) or adulthood. Common problems in juvenile and adult forms of Alexander disease include speech abnormalities, swallowing difficulties, and poor coordination.[1][2] Alexander disease is caused by mutations in the GFAP gene. While this condition is inherited in an autosomal dominant fashion, most cases result from new mutations in the gene.[1]


The symptoms of Alexander disease vary depending on the form of the condition (neonatal, infantile, juvenile, and adult). Even within the different forms there may be huge differences in respect to symptoms and severity:[3][2][4][1]

  • Neonatal form Leads to severe disability or death within two years. Characteristics include seizures, hydrocephalus, severe motor and intellectual disability.
  • Infantile form The most common type of Alexander disease. It has an onset during the first two years of life. Usually there are both mental and physical developmental delays, followed by the loss of developmental milestones, an abnormal increase in head size, and seizures.
  • Juvenile form Less common and has an onset between the ages of two and thirteen. These children may have excessive vomiting, difficulty swallowing and speaking, poor coordination, and loss of motor control.
  • Adult form Rare and is generally the most mild. Onset can be anywhere from the late teens to very late in life. In some cases the symptoms mimic those of Parkinson disease or multiple sclerosis.

The United Leukodystrophy Foundation provides additional details related to the symptoms of this condition.

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
30%-79% of people have these symptoms
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
Bulbar signs
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

Diffuse demyelination of the cerebral white matter
Too much cerebrospinal fluid in the brain
Increased CSF protein
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

Progressive macrocephaly
Progressively abnormally enlarging cranium
Progressively abnormally enlarging skull

[ more ]

Involuntary muscle stiffness, contraction, or spasm


The disease is caused by changes (mutations in the GFAP gene in about 90% of cases. This gene provides the instructions for making a protein called glial fibrillary acidic protein (GFAP). GFAP is a normal part of the brain, but it is not clear how mutations in the gene cause the disease. In most cases, the mutations are new in the family (de novo) and are not inherited from the parents. A small number of people who are thought to have Alexander disease are not found to have a mutation in the GFAP gene, which suggests that there may be other causes of Alexander disease that have yet to be identified.[1]


No specific therapy is currently available for Alexander disease. Management is supportive and includes attention to general care, physical and occupational therapy, nutritional requirements, antibiotic treatment for any infection, and antiepileptic drugs (AED) for seizure control.[4]

Physical and occupational therapy and speech therapy may be recommended depending on the specific signs and symptoms present. Physical and occupational therapy may be indicated in people with developmental and language delays.

Management Guidelines


    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Providing General Support

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Alexander disease. Click on the link to view a sample search on this topic.


          1. Alexander disease. Genetics Home Reference. October, 2015; https://ghr.nlm.nih.gov/condition=alexanderdisease. Accessed 10/31/2015.
          2. Alexander disease. National Institute of Neurological Disorders and Stroke (NINDS). October, 22, 2012; https://www.ninds.nih.gov/disorders/alexander_disease/alexander_disease.htm. Accessed 10/31/2015.
          3. Alexander Disease. United Leukodystrophy Foundation. https://ulf.org/alexander-disease#. Accessed 10/31/2015.
          4. Gorospe JR. Alexander Disease. GeneReviews. January 8, 2015; https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=alexander. Accessed 10/31/2015.

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