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Alexander disease

 

Alexander disease

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

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

Contents

  • Cause 1
  • Clinical features 2
  • Pathology 3
  • Diagnosis 4
  • Occurrence and prevalence 5
  • Treatment 6
  • Prognosis 7
  • See also 8
  • References 9
  • External links 10

Cause

Alexander disease is a genetic disorder affecting the midbrain and cerebellum of the central nervous system. 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% chance of inheriting the condition, if the parent is heterozygotic. However, most cases arise de novo as the result of sporadic mutations.[2]

Alexander disease belongs to leukodystrophies, a group of diseases that affect the 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 do not share the distribution or concentration of other diseases and disorders.[3]

Clinical features

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

Pathology

Alexander disease causes the gradual loss of bodily functions and the ability to talk. It also causes an overload of long chain fatty acids in the brain which the destroy the myelin sheath. The cause of Alexander disease is a mutation in the gene encoding glial fibrillary acidic protein.[2][3][4][5][9]

A CT scan shows:

Diagnosis

It is possible to detect the signs of Alexander disease with magnetic resonance imaging (MRI), 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 MRI.[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

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

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

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

See also

References

  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.  
  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.  
  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.  
  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.  
  10. ^ Labauge P (June 2009). "Magnetic resonance findings in leucodystrophies and MS". Int MS J 16 (2): 47–56.  
  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.  
  12. ^ Johnson AB (2002). "Alexander disease: a review and the gene". Int. J. Dev. Neurosci. 20 (3-5): 391–4.  
  13. ^ Sawaishi Y (August 2009). "Review of Alexander disease: beyond the classical concept of leukodystrophy". Brain Dev. 31 (7): 493–8.  
  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.  
  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.  
  16. ^ Messing A, LaPash Daniels CM, Hagemann TL (October 2010). "Strategies for treatment in Alexander disease". Neurotherapeutics 7 (4): 507–15.  

External links

  • OMIM entries on Alexander disease


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