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Genetics Home Reference: your guide to understanding genetic conditions
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Alexander disease

Reviewed November 2008

What is Alexander disease?

Alexander disease is a rare disorder of the nervous system. It is one of a group of disorders, called leukodystrophies, that involve the destruction of myelin. Myelin is the fatty covering that insulates nerve fibers and promotes the rapid transmission of nerve impulses. If myelin is not properly maintained, the transmission of nerve impulses could be disrupted. As myelin deteriorates in leukodystrophies such as Alexander disease, nervous system functions are impaired.

Most cases of Alexander disease begin before age 2 and are described as the infantile form. Signs and symptoms of the infantile form typically include an enlarged brain and head size (megalencephaly), seizures, stiffness in the arms and/or legs (spasticity), intellectual disability, and developmental delay. Less frequently, onset occurs later in childhood (the juvenile form) or in adulthood. Common problems in juvenile and adult forms of Alexander disease include speech abnormalities, swallowing difficulties, seizures, and poor coordination (ataxia). Rarely, a neonatal form of Alexander disease occurs within the first month of life and is associated with severe intellectual disability and developmental delay, a buildup of fluid in the brain (hydrocephalus), and seizures.

Alexander disease is also characterized by abnormal protein deposits known as Rosenthal fibers. These deposits are found in specialized cells called astroglial cells, which support and nourish other cells in the brain and spinal cord (central nervous system).

How common is Alexander disease?

The prevalence of Alexander disease is unknown. About 500 cases have been reported since the disorder was first described in 1949.

What genes are related to Alexander disease?

Mutations in the GFAP gene cause Alexander disease. The GFAP gene provides instructions for making a protein called glial fibrillary acidic protein. Several molecules of this protein bind together to form intermediate filaments, which provide support and strength to cells. Mutations in the GFAP gene lead to the production of a structurally altered glial fibrillary acidic protein. The altered protein is thought to impair the formation of normal intermediate filaments. As a result, the abnormal glial fibrillary acidic protein likely accumulates in astroglial cells, leading to the formation of Rosenthal fibers, which impair cell function. It is not well understood how impaired astroglial cells contribute to the abnormal formation or maintenance of myelin, leading to the signs and symptoms of Alexander disease.

Related Gene(s)

Changes in this gene are associated with Alexander disease.

  • GFAP

How do people inherit Alexander disease?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Most cases result from new mutations in the gene. These cases occur in people with no history of the disorder in their family. Rarely, an affected person inherits the mutation from one affected parent.

Where can I find information about diagnosis or management of Alexander disease?

These resources address the diagnosis or management of Alexander disease and may include treatment providers.

  • Gene Review: Alexander Disease (http://www.ncbi.nlm.nih.gov/books/NBK1172/)
  • Genetic Testing Registry: Alexander's disease (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0270726)
  • MedlinePlus Encyclopedia: Myelin (http://www.nlm.nih.gov/medlineplus/ency/article/002261.htm)

You might also find information on the diagnosis or management of Alexander disease in Educational resources (http://www.ghr.nlm.nih.gov/condition/alexander-disease/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/alexander-disease/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Alexander disease?

You may find the following resources about Alexander disease helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Alexander disease?

  • Alexander's disease
  • ALX
  • AxD
  • demyelinogenic leukodystrophy
  • dysmyelinogenic leukodystrophy
  • fibrinoid degeneration of astrocytes
  • leukodystrophy with Rosenthal fibers

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Alexander disease?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Alexander disease?

astrocytes ; ataxia ; autosomal ; autosomal dominant ; cell ; central nervous system ; developmental delay ; disability ; fibrillary ; gene ; hydrocephalus ; inherited ; intermediate filaments ; juvenile ; leukodystrophy ; megalencephaly ; mutation ; neonatal ; nervous system ; prevalence ; protein ; spasticity

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Gene Review: Alexander Disease (http://www.ncbi.nlm.nih.gov/books/NBK1172/)
  • Gorospe JR, Maletkovic J. Alexander disease and megalencephalic leukoencephalopathy with subcortical cysts: leukodystrophies arising from astrocyte dysfunction. Ment Retard Dev Disabil Res Rev. 2006;12(2):113-22. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16807904?dopt=Abstract)
  • Li R, Johnson AB, Salomons G, Goldman JE, Naidu S, Quinlan R, Cree B, Ruyle SZ, Banwell B, D'Hooghe M, Siebert JR, Rolf CM, Cox H, Reddy A, Gutiérrez-Solana LG, Collins A, Weller RO, Messing A, van der Knaap MS, Brenner M. Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease. Ann Neurol. 2005 Mar;57(3):310-26. (http://www.ncbi.nlm.nih.gov/pubmed/15732097?dopt=Abstract)
  • Omary MB, Coulombe PA, McLean WH. Intermediate filament proteins and their associated diseases. N Engl J Med. 2004 Nov 11;351(20):2087-100. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15537907?dopt=Abstract)
  • Quinlan RA, Brenner M, Goldman JE, Messing A. GFAP and its role in Alexander disease. Exp Cell Res. 2007 Jun 10;313(10):2077-87. Epub 2007 Apr 6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17498694?dopt=Abstract)
  • van der Knaap MS, Ramesh V, Schiffmann R, Blaser S, Kyllerman M, Gholkar A, Ellison DW, van der Voorn JP, van Dooren SJ, Jakobs C, Barkhof F, Salomons GS. Alexander disease: ventricular garlands and abnormalities of the medulla and spinal cord. Neurology. 2006 Feb 28;66(4):494-8. (http://www.ncbi.nlm.nih.gov/pubmed/16505300?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: November 2008
Published: July 21, 2014