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Adult-onset Alexander disease

Report on a family

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Abstract

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.

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Authors and Affiliations

  1. Clinical Neurophysiology, Scientific Institute of Montescano IRCCS 'Fondazione S.Maugeri', via per Montescano, 27040, Montescano, PV, Italy

    P. Balbi MD, R. Casale MD & C. Fundarò MD

  2. Laboratory of Medical Genetics, U.O. Genetica Medica University of Bologna Policlinico S. Orsola-Malpighi – Pad. 11, Via Massarenti n° 9, 40138, Bologna, Italy

    M. Seri MD

  3. Laboratory of Molecular Genetics, 'G. Gaslini' Institute, Largo G. Gaslini 5, 16147, Genova, Italy

    I. Ceccherini PhD & F. Caroli BS

  4. Neuroradiological Department, Neurological Institute IRCCS 'Fondazione C. Mondino', via Mondino 2, 27100, Pavia, Italy

    C. Uggetti MD

  5. Dept. of Neurological Science, 'Federico II' University of Naples, via Sergio Pansini 5, 80135, Naples, Italy

    L. Santoro MD

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  1. P. Balbi MD
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  2. M. Seri MD
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Correspondence to P. Balbi MD.

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Balbi, P., Seri, M., Ceccherini, I. et al. Adult-onset Alexander disease. J Neurol 255, 24–30 (2008). https://doi.org/10.1007/s00415-007-0654-0

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  • DOI: https://doi.org/10.1007/s00415-007-0654-0

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