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Diseases

Genetic and Rare Diseases Information Center (GARD)

Alexander disease


Other Names for this Disease
  • Alexanders leukodystrophy
  • Megalencephaly in infancy accompanied by progressive spasticity and dementia
  • AxD
Related Diseases
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Your Question

My step-daughter was diagnosed with Alexander Disease less than a year ago. She is 2 years old.We were recently told that the disease is spreading to her pituitary gland.What impact will this have on the progression of the disease?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is Alexander disease?

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, mental retardation, 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]
Last updated: 12/29/2015

What are the signs and symptoms of Alexander disease?

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.

Last updated: 12/29/2015

What is the prognosis for individuals diagnosed with Alexander disease?

The prognosis for individuals with Alexander disease is generally poor and typically depends of the specific form. People with the neonatal form usually have the worst prognosis. Most children with the infantile form do not survive past the age of 6. The juvenile and adult forms of the disorder have a slower, more lengthy course. The adult form varies greatly and, in some cases, there are no symptoms.[2]
Last updated: 12/29/2015

What impact might involvement of Alexander disease in the pituitary play in the disease process?

Our search of the medical literature found just one case report of Alexander disease which involved issues with the pituitary. Case reports describe and discuss the symptoms/clinical aspects of one person with a certain condition.  It is important to keep in mind that the clinical findings described in case reports are based only on specific people and may differ from one person with the disorder to the next.  We strongly recommend you discuss any articles that interest you with your physician.

The case report we found described an individual with symptoms that began as an infant. Symptoms started with seizures and a condition called ventriculomegaly, which is when fluid-filled sacs in the brain are larger than normal. This person also had mild psychomotor delay (slowing down of physical movements) which became worse with time. Over time, this individual also developed weakness on one side of the body (hemiparesis) and developed tightening and/or stiffening of the muscles (spasticity).

People with Alexander disease have abnormal protein deposits known as Rosenthal fibers. These deposits are made of the protein GFAP, which are found in specialized cells called glial cells. Glial cells are supposed to support and nourish other cells in the brain and spinal cord (central nervous system). These Rosenthal fibers are not seen in healthy people. It is the presence of these Rosenthal fibers that cause Alexander disease. In this case study, these Rosenthal fibers were also found in the neurohypophyseal pituicytes. A pituicyte is a glial cell of the pituitary. The child died at age 12. To read more about the case study, click here.    

You can access this and other relevant articles on Alexander disease through PubMed, a searchable database of biomedical journal articles. Although not all of the articles are available for free online, most articles listed in PubMed have a summary available. To obtain the full article, contact a medical/university library or your local library for interlibrary loan. You can also order articles online through the publisher’s Web site. Using 'Alexander disease[ti]' as your search term should help you locate articles. Use the advanced search feature to narrow your search results. Click here to view a search.
http://www.ncbi.nlm.nih.gov/PubMed

The National Library of Medicine (NLM) Web site has a page for locating libraries in your area that can provide direct access to these journals (print or online). The web page also describes how you can get these articles through interlibrary loan and Loansome Doc (an NLM document-ordering service). You can access this page by clicking here. You can also contact the NLM toll-free at 888-346-3656 to locate libraries in your area.

Last updated: 1/11/2016

References
Other Names for this Disease
  • Alexanders leukodystrophy
  • Megalencephaly in infancy accompanied by progressive spasticity and dementia
  • AxD
Related Diseases
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.