Advertisement

Journal of Neurology

, 254:1390 | Cite as

An adult form of Alexander disease: a novel mutation in glial fibrillary acidic protein

  • K. OhnariEmail author
  • M. Yamano
  • T. Uozumi
  • T. Hashimoto
  • S. Tsuji
  • M. Nakagawa
ORIGINAL COMMUNICATION

Abstract

Glial fibrillary acidic protein (GFAP) mutation has been reported in Alexander disease. We report a patient with the adult form of Alexander disease who shows a novel mutation in GFAP. This case presented with progressive dysarthria, dysphagia and spastic gait on the right side. Brain and spinal cord MRI showed marked atrophy of the medulla oblongata and spinal cord. Abnormal high signal intensities in the ventral medulla oblongata were detected bilaterally. There were no white matter lesions or contrast enhancing lesions. Recently, there have been reports of patients with a juvenile form of Alexander disease presenting with atrophy or signal abnormalities of the medulla or spinal cord. Atrophy of the medulla and spinal cord have specifically been described as suggestive of Alexander disease [1]. Sequence analysis of the GFAP gene of this patient showed a heterozygous c.221T>C mutation, predicting a p.M74T amino acid change. In all patients suspected of Alexander disease on the basis of MRI findings, GFAP analysis is necessary to confirm the diagnosis.

Key words

Alexander disease GFAP 

References

  1. 1.
    Van der Knaap MS, Ramesh V, et al. (2006) Alexander disease Ventricular garlands and abnormalities of medulla and spinal cord. Neurology 66:494-98CrossRefPubMedGoogle Scholar
  2. 2.
    Alexander WS (1949) Progressive fibrinoid degeneration of fibrillary astrocytes associated with mental retardation in a hydrocephalic infant. Brain 72:373-81CrossRefPubMedGoogle Scholar
  3. 3.
    Iwaki T, Iwaki A, et al. (1993) αB-crystallin and 27-kd heat shock protein are regulated by stress condition in the central nerve system and nervous system and accumulate in Rosenthal fibers. Am J Pathol 143:487-95PubMedGoogle Scholar
  4. 4.
    Brenner M, Johnson AB, et al. (2001) Mutation in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Nat Genet 27:117-20CrossRefPubMedGoogle Scholar
  5. 5.
    Kawaguchi Y, Okamoto T, et al. (1994) CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet 8:221-27CrossRefPubMedGoogle Scholar
  6. 6.
    David G, Abbas N, et al. (1997) Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nat Genet 7:65-0CrossRefGoogle Scholar
  7. 7.
    Sasaki H,Yabe I, et al. (2000) Prevalence of triplet repeat expansion in ataxia patients from Hokkaido, the northernmost island of Japan. J Neurol Sci 175:45-1CrossRefPubMedGoogle Scholar
  8. 8.
    Li R, Johnson A, et al. (2005) Glial fibrillary acidic protein mutation in infantile, Juvenile, and adult forms of Alexander disease. Ann Neurol 57: 310-26CrossRefPubMedGoogle Scholar
  9. 9.
    Gorospe JR, Naidu S, et al. (2002) Molecular findings in symptomatic and pre-symptomatic Alexander disease patients. Neurology 58:1494-500PubMedGoogle Scholar
  10. 10.
    Okamoto Y, Mitsuyama H, et al. (2002) Autosomal dominant palatal myoclonus and spinal cord atrophy. J Neurol Sci 195:71-6CrossRefPubMedGoogle Scholar
  11. 11.
    Namekawa M, Takiyama Y, et al. (2002) Identification of GFAP gene mutation in hereditary adult-onset Alexander's disease. Ann Neurol 52:779-85CrossRefPubMedGoogle Scholar
  12. 12.
    Kinoshita T, Imaizumi T, et al. (2003) A case of adult-onset Alexander disease with Arg416Trp human glial fibrillary acidic protein gene mutation. Neurosci Lett 350:169-72CrossRefPubMedGoogle Scholar
  13. 13.
    Brockmann K, Meins M, et al. (2003) A novel GFAP mutation and disseminated white matter lesion: adult Alexander disease? Eur Neurol 50: 100-05CrossRefPubMedGoogle Scholar
  14. 14.
    Thyagarajan D, Chataway T, et al. (2004) Dominantly-inherited adultonset Leukodystrophy with palatal tremor caused by a mutation in the glial fibrillary acidic protein gene. Mov Disord 19:1244-248CrossRefPubMedGoogle Scholar
  15. 15.
    Van der Knaap MS, Salomons G, et al. (2005) Unusual variants of Alexander's disease. Ann Neurol 57:327-38CrossRefPubMedGoogle Scholar
  16. 16.
    Stumpf E, Masson H, et al. (2003) Adult Alexander disease with autosomal dominant transmission. Arch Neurol 60:1307-312CrossRefPubMedGoogle Scholar
  17. 17.
    Rodriguez D, Gauthier F, et al. (2001) Infantile Alexander disease: spectrum of GFAP mutations and genotype-phenotype correlation. Am J Hum Genet 69:1134-140CrossRefPubMedGoogle Scholar
  18. 18.
    Van der Knaap MS,Naidu S, et al. (2001) Alexander disease: diagnosis with MR imaging. Am J Neuroradiol 22:541-52PubMedGoogle Scholar

Copyright information

© Steinkopff-Verlag 2007

Authors and Affiliations

  • K. Ohnari
    • 1
    Email author
  • M. Yamano
    • 1
  • T. Uozumi
    • 1
  • T. Hashimoto
    • 1
  • S. Tsuji
    • 1
  • M. Nakagawa
    • 2
  1. 1.Dept. of NeurologyUniversity of Occupational and Environmental Health, School of Medicine Yahatanishi-kuKitakyushuJapan
  2. 2.Research Institute for Neurological Diseases and Geriatrics, Dept. of Neurology and GerontologyKyoto Prefectural University of MedicineKyotoJapan

Personalised recommendations