Child's Nervous System

, Volume 28, Issue 12, pp 2029–2031

Alexander’s disease: reassessment of a neonatal form

  • Navneet Singh
  • Catherine Bixby
  • Denzil Etienne
  • R. Shane Tubbs
  • Marios Loukas
Review Paper

Abstract

Introduction

Alexander disease is a disorder caused by a mutation and accumulation of the glial fibrillary acidic protein. Currently, three subtypes are acknowledged: an infantile, a juvenile, and an adult form. However, onset early in infancy or in the prenatal period has been shown to present with a uniform pattern of symptoms—suggesting the presence of a distinct neonatal form of the disease.

Results and discussion

Though the neonatal form of Alexander disease is not well acknowledged, a uniform and distinct presentation of the disease in neonates has been observed, suggesting the need for a different course of identification and treatment. Clinical presentation of the neonatal form is distinguished by leukodystrophy and generalized, frequent, and intractable seizures. While the infantile form presents with ataxia, hyperreflexia, and other upper motor neuron symptoms, none of these has been observed in the neonatal form. In the diagnosis of neonatal Alexander disease, it is essential to rule out other causes of leukodystrophy and the presence of neoplasms.

Keywords

Alexander disease Neonatal Infantile Leukodystrophy 

References

  1. 1.
    Brenner M, Johnson AB, Boespflug-Tanguy O, Rodriguez D, Goldman JE, Messing A (2001) Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Nat Gen 27:117–120CrossRefGoogle Scholar
  2. 2.
    Gorospe JR (1993) Alexander disease. In: Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP (eds) GeneReviews. Seattle (WA)Google Scholar
  3. 3.
    Hsiao VC, Tian R, Long H, Der Perng M, Brenner M, Quinlan RA, Goldman JE (2005) Alexander-disease mutation of GFAP causes filament disorganization and decreased solubility of GFAP. J Cell Sci 118(Pt 9):2057–2065PubMedCrossRefGoogle Scholar
  4. 4.
    Johnson AB, Brenner M (2003) Alexander’s disease: clinical, pathologic, and genetic features. J Child Neurol 18:625–632PubMedCrossRefGoogle Scholar
  5. 5.
    Messing A, Daniels CM, Hagemann TL (2010) Strategies for treatment in Alexander disease. Neurotherapeutics 7:507–515PubMedCrossRefGoogle Scholar
  6. 6.
    Pridmore CL, Baraitser M, Harding B, Boyd SG, Kendall B, Brett EM (1993) Alexander’s disease: clues to diagnosis. J Child Neurol 8:134–144PubMedCrossRefGoogle Scholar
  7. 7.
    Prust M, Wang J, Morizono H, Messing A, Brenner M, Gordon E, Hartka T, Sokohl A, Schiffmann R, Gordish-Dressman H, Albin R, Amartino H, Brockman K, Dinopoulos A, Dotti MT, Fain D, Fernandez R, Ferreira J, Fleming J, Gill D, Griebel M, Heilstedt H, Kaplan P, Lewis D, Nakagawa M, Pedersen R, Reddy A, Sawaishi Y, Schneider M, Sherr E, Takiyama Y, Wakabayashi K, Gorospe JR, Vanderver A (2011) GFAP mutations, age at onset, and clinical subtypes in Alexander disease. Neurology 77:1287–1294PubMedCrossRefGoogle Scholar
  8. 8.
    Rodriguez D, Gauthier F, Bertini E, Bugiani M, Brenner M, N’Guyen S, Goizet C, Gelot A, Surtees R, Pedespan JM, Hernandorena X, Troncoso M, Uziel G, Messing A, Ponsot G, Pham-Dinh D, Dautigny A, Boespflug-Tanguy O (2001) Infantile Alexander disease: spectrum of GFAP mutations and genotype–phenotype correlation. Am J Hum Genet 69:1134–1140PubMedCrossRefGoogle Scholar
  9. 9.
    Russo LS Jr, Aron A, Anderson PJ (1976) Alexander’s disease: a report and reappraisal. Neurology 26:607–614PubMedCrossRefGoogle Scholar
  10. 10.
    Springer S, Erlewein R, Naegele T, Becker I, Auer D, Grodd W, Krageloh-Mann I (2000) Alexander disease—classification revisited and isolation of a neonatal form. Neuropediatrics 31:86–92PubMedCrossRefGoogle Scholar
  11. 11.
    Townsend JJ, Wilson JF, Harris T, Coulter D, Fife R (1985) Alexander’s disease. Acta Neuropathol 67:163–166PubMedCrossRefGoogle Scholar
  12. 12.
    van der Knaap MS, Naidu S, Breiter SN, Blaser S, Stroink H, Springer S, Begeer JC, van Coster R, Barth PG, Thomas NH, Valk J, Powers JM (2001) Alexander disease: diagnosis with MR imaging. AJNR 22:541–552PubMedGoogle Scholar
  13. 13.
    van der Knaap MS, Salomons GS, Li R, Franzoni E, Gutierrez-Solana LG, Smit LM, Robinson R, Ferrie CD, Cree B, Reddy A, Thomas N, Banwell B, Barkhof F, Jakobs C, Johnson A, Messing A, Brenner M (2005) Unusual variants of Alexander’s disease. Ann Neurol 57:327–338PubMedCrossRefGoogle Scholar
  14. 14.
    Van Poppel K, Broniscer A, Patay Z, Morris EB (2009) Alexander disease: an important mimicker of focal brainstem glioma. Pediat Blood Cancer 53:1355–1356CrossRefGoogle Scholar
  15. 15.
    Vazquez E, Macaya A, Mayolas N, Arevalo S, Poca MA, Enriquez G (2008) Neonatal Alexander disease: MR imaging prenatal diagnosis. AJNR 29:1973–1975PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Navneet Singh
    • 1
  • Catherine Bixby
    • 1
  • Denzil Etienne
    • 1
  • R. Shane Tubbs
    • 3
  • Marios Loukas
    • 1
    • 2
  1. 1.Department of Anatomical Sciences, School of MedicineSt George’s UniversityWest IndiesGrenada
  2. 2.Department of AnatomyVarmia and Mazuria Medical SchoolOlsztynPoland
  3. 3.Pediatric NeurosurgeryChildren’s HospitalBirminghamUSA

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