Alexander disease

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Alexander disease
Classification and external resources
Alexander autopsy.jpg
Brain of a 4-year-old boy with Alexander disease showing macroencephaly and periventricular demyelinisation (note brownish discoloration around the cerebral ventricles)
ICD-10 E75.2
ICD-9 331.89
OMIM 203450 137780 137780 203450
MeSH D038261
GeneReviews

Alexander disease, also known as fibrinoid leukodystrophy, is a slowly progressing and fatal neurodegenerative disease. It is a very rare disorder which results from a genetic mutation and mostly affects infants and children, causing developmental delay and changes in physical characteristics.[1][2][3]

Cause[edit]

Alexander disease is a genetic disorder affecting the central nervous system (midbrain and cerebellum). It is caused by mutations in the gene for glial fibrillary acidic protein (GFAP)[4][5][6] that maps to chromosome 17q21. It is inherited in an Autosomal Dominant manner, such that the child of a parent with the disease has a 50/50 chance of inheriting the condition[2]

Alexander disease belongs to leukodystrophies, a group of diseases which affect growth or development of the myelin sheath. The destruction of white matter in the brain is accompanied by the formation of fibrous, eosinophilic deposits known as Rosenthal fibers.[2][3][7] Rosenthal fibers appear not to be present in healthy people,[3][8] but occur in specific diseases, like some forms of cancer.[3][8] The Rosenthal fibers found in Alexander disease are not distributed in the same areas or as concentrated when compared to other diseases and disorders.[3]

Clinical features[edit]

Delays in development of some physical, psychological and behavioral skills, progressive enlargement of the head (macrocephaly), seizures, spasticity, in some cases also hydrocephalus, IIH, dementia.[2]

Pathology[edit]

Alexander disease causes the affected person to slowly begin to lose body function and eventually the ability to talk. It also causes an overload of long chain fatty acids that the body cannot dispose of. This overload of fatty acids builds up in the brain and destroys the myelin sheath. The cause of Alexander disease is a mutation in the gene encoding glial fibrillary acidic protein.[2][3][4][5][9]

CT shows:

Diagnosis[edit]

It is possible to detect the signs of Alexander disease with Magnetic Resonance Imaging, which looks for specific changes in the brain that may be tell-tale signs for the disease.[10][11] It is even possible to detect adult-onset Alexander disease with MR imaging.[9] Alexander disease may also be revealed by genetic testing for the known cause of Alexander disease.[12][13] A rough diagnosis may also be made through revealing of clinical symptoms including, enlarged head size, along with radiological studies, and negative tests for other leukodystrophies.[8]

Occurrence and prevalence[edit]

Its occurrence is very rare. The infantile form from birth to 2 years of age.[6] The average duration of the infantile form of the illness is usually about 3 years. Onset of the juvenile form presents between two and twelve years of age.[6] Duration of this form is in most cases about 6 years. The Adult form from twelve years and older.[6] In younger patients, seizures, megalencephaly, developmental delay, and spasticity are usually present. Neonatal onset is also reported.[14] Onset in adults is least frequent. In older patients, bulbar or pseudobulbar symptoms and spasticity predominate. Symptoms of the adult form may also resemble multiple sclerosis.[2]

There are no more than 500 reported cases.[2]

Treatment[edit]

There is currently no cure, or standard procedure taken for treatment.[2][3] A bone marrow transplant has been attempted on a child, but did not cause the patient's condition to improve.[15][16]

Prognosis[edit]

The prognosis is generally poor. With early onset, death usually occurs within 10 years after the onset of symptoms. Usually, the later the disease occurs, the slower its course is.[2][3]

See also[edit]

References[edit]

  1. ^ "MUTATION KEY TO ALEXANDER DISEASE" - United Press International
  2. ^ a b c d e f g h i GeneReviews/NCBI/NIH/UW entry on Alexander disease
  3. ^ a b c d e f g h alexander_disease at NINDS
  4. ^ a b Li R, Messing A, Goldman JE, Brenner M (2002). "GFAP mutations in Alexander disease". Int. J. Dev. Neurosci. 20 (3-5): 259–68. doi:10.1016/s0736-5748(02)00019-9. PMID 12175861. 
  5. ^ a b Quinlan RA, Brenner M, Goldman JE, Messing A (June 2007). "GFAP and its role in Alexander disease". Exp. Cell Res. 313 (10): 2077–87. doi:10.1016/j.yexcr.2007.04.004. PMC 2702672. PMID 17498694. 
  6. ^ a b c d Messing A, Brenner M, Feany MB, Nedergaard M, Goldman JE (April 2012). "Alexander disease". J. Neurosci. 32 (15): 5017–23. doi:10.1523/JNEUROSCI.5384-11.2012. PMC 3336214. PMID 22496548. 
  7. ^ "Cause of brain disease found" -BBC News
  8. ^ a b c http://www.ulf.org/types/Alexander.html
  9. ^ a b Farina L, Pareyson D, Minati L, et al. (June 2008). "Can MR imaging diagnose adult-onset Alexander disease?". AJNR Am J Neuroradiol 29 (6): 1190–6. doi:10.3174/ajnr.A1060. PMID 18388212. 
  10. ^ Labauge P (June 2009). "Magnetic resonance findings in leucodystrophies and MS". Int MS J 16 (2): 47–56. PMID 19671368. 
  11. ^ van der Knaap MS, Naidu S, Breiter SN, et al. (March 2001). "Alexander disease: diagnosis with MR imaging". AJNR Am J Neuroradiol 22 (3): 541–52. PMID 11237983. 
  12. ^ Johnson AB (2002). "Alexander disease: a review and the gene". Int. J. Dev. Neurosci. 20 (3-5): 391–4. doi:10.1016/S0736-5748(02)00045-X. PMID 12175878. 
  13. ^ Sawaishi Y (August 2009). "Review of Alexander disease: beyond the classical concept of leukodystrophy". Brain Dev. 31 (7): 493–8. doi:10.1016/j.braindev.2009.03.006. PMID 19386454. 
  14. ^ Singh N, Bixby C, Etienne D, Tubbs RS, Loukas M (December 2012). "Alexander's disease: reassessment of a neonatal form". Childs Nerv Syst 28 (12): 2029–31. doi:10.1007/s00381-012-1868-8. PMID 22890470. 
  15. ^ Staba MJ, Goldman S, Johnson FL, Huttenlocher PR (August 1997). "Allogeneic bone marrow transplantation for Alexander's disease". Bone Marrow Transplant. 20 (3): 247–9. doi:10.1038/sj.bmt.1700871. PMID 9257894. 
  16. ^ Messing A, LaPash Daniels CM, Hagemann TL (October 2010). "Strategies for treatment in Alexander disease". Neurotherapeutics 7 (4): 507–15. doi:10.1016/j.nurt.2010.05.013. PMC 2948554. PMID 20880512. 

External links[edit]