Journal of Neurology

, Volume 255, Issue 1, pp 24–30 | Cite as

Adult-onset Alexander disease

Report on a family
  • P. BalbiEmail author
  • M. Seri
  • I. Ceccherini
  • C. Uggetti
  • R. Casale
  • C. Fundarò
  • F. Caroli
  • L. Santoro


Pathogenic, dominant, de novo missense mutations in the glial fibrillary acidic protein (GFAP) have been found in the three subtypes of infantile, juvenile and adult Alexander disease.

Here we describe four members of an Italian family (32 to 66-yearsold, 2 women and 2 men) affected by adult Alexander disease, the least common and the most clinically variable form.Direct sequencing of all coding regions of the GFAP gene, neurological examination and brain MRI were performed.

Two novel missense mutations were found involving two very close codons, c.[988C > G, 994G > A], leading to p.[Arg330Gly, Glu332Lys]. Clinically, two members exhibited pseudo-bulbar signs, gait ataxia and spasticity, one showed a severe cranial sensory symptomatology, and one subject was asymptomatic.Medulla and cervical cord atrophy was present in all of them on MRI.

Although adult Alexander disease shows a wide clinical variability, a more frequent pattern can be identified characterized by bulbar or pseudo-bulbar signs, gait ataxia, and spasticity, and including on MRI medulla and cervical cord atrophy. Our findings also confirm that the clinical spectrum of adult Alexander disease includes cases without overt neurological involvement and with minimal brain MRI alterations.

Key words

Alexander disease GFAP mutations neurodegenerative disorder signs and symptoms 


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Copyright information

© Steinkopff-Verlag 2007

Authors and Affiliations

  • P. Balbi
    • 1
    Email author
  • M. Seri
    • 2
  • I. Ceccherini
    • 3
  • C. Uggetti
    • 4
  • R. Casale
    • 1
  • C. Fundarò
    • 1
  • F. Caroli
    • 3
  • L. Santoro
    • 5
  1. 1.Clinical NeurophysiologyScientific Institute of Montescano IRCCS 'Fondazione S.Maugeri'Montescano, PVItaly
  2. 2.Laboratory of Medical GeneticsU.O. Genetica Medica University of Bologna Policlinico S. Orsola-Malpighi – Pad. 11BolognaItaly
  3. 3.Laboratory of Molecular Genetics'G. Gaslini' InstituteGenovaItaly
  4. 4.Neuroradiological DepartmentNeurological Institute IRCCS 'Fondazione C. Mondino'PaviaItaly
  5. 5.Dept. of Neurological Science'Federico II' University of NaplesNaplesItaly

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