Abstract  Mutations in the mitofusin 2 (MFN2) gene are a major cause of primary axonal Charcot- Marie-Tooth (CMT) neuropathy. This study aims at further characterization of cerebral white matter alterations observed in patients with MFN2 mutations. Molecular genetic, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) investigations were performed in four unrelated patients aged 7 to 38 years with early onset axonal CMT neuropathy. Three distinct and so far undescribed MFN2 mutations were detected. Two patients had secondary macrocephaly and mild diffuse predominantly periventricular white matter alterations on MRI. In addition, one boy had symmetrical T2-hyperintensities in both thalami. Two patients had optic atrophy, one of them with normal MRI. In three patients proton MRS revealed elevated concentrations of total N-acetyl compounds (neuronal marker), total creatine (found in all cells) and myo-inositol (astrocytic marker) in cerebral white and gray matter though with regional variation. These alterations were most pronounced in the two patients with abnormal MRI. DTI of these patients revealed mild reductions of fractional anisotropy and mild increase of mean diffusivity in white matter. The present findings indicate an enhanced cellular density in cerebral white matter of MFN2 neuropathy which is primarily due to a reactive gliosis without axonal damage and possibly accompanied by mild demyelination. Content Type Journal ArticleCategory ORIGINAL COMMUNICATIONDOI 10.1007/s00415-008-0847-1Authors Knut Brockmann, Georg August University Dept. of Pediatrics and Pediatric Neurology Robert-Koch-Str. 40 37075 Göttingen GermanySteffi Dreha-Kulaczewski, Georg August University Dept. of Pediatrics and Pediatric Neurology Robert-Koch-Str. 40 37075 Göttingen GermanyPeter Dechent, Georg August University MR Research in Neurology and Psychiatry Göttingen GermanyCarsten Bönnemann, and University of Pennsylvania, School of Medicine Division of Neurology, The Children’s Hospital of Philadelphia Philadelphia USAGunther Helms, Georg August University MR Research in Neurology and Psychiatry Göttingen GermanyMarten Kyllerman, Sahlgrenska University Dept. of Neuropediatrics, Queen Silvia Children’s Hospital Göteborg SwedenWolfgang Brück, Georg August University Dept. of Neuropathology Göttingen GermanyJens Frahm, am Max-Planck-Institut für biophysikalische Chemie Biomedizinische NMR Forschungs GmbH Göttingen GermanyKathrin Huehne, Friedrich Alexander University of Erlangen-Nuremberg Institute of Human Genetics Erlangen GermanyJutta Gärtner, Georg August University Dept. of Pediatrics and Pediatric Neurology Robert-Koch-Str. 40 37075 Göttingen GermanyBernd Rautenstrauss, Friedrich Alexander University of Erlangen-Nuremberg Institute of Human Genetics Erlangen Germany Journal Journal of NeurologyOnline ISSN 1432-1459Print ISSN 0340-5354 (Source: Journal of Neurology)

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