Cerebral involvement in axonal Charcot-Marie-Tooth neuropathy caused by mitofusin2 mutations.
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.
Brockmann
Knut
K
Dept. of Pediatrics and Pediatric Neurology, Georg August University, Robert-Koch-Str. 40, 37075 Göttingen, Germany. kbrock@med.uni-goettingen.de
Dreha-Kulaczewski
Steffi
S
Dechent
Peter
P
Bönnemann
Carsten
C
Helms
Gunther
G
Kyllerman
Marten
M
Brück
Wolfgang
W
Frahm
Jens
J
Huehne
Kathrin
K
Gärtner
Jutta
J
Rautenstrauss
Bernd
B
D000293:Adolescent; D000328:Adult; D001369:Axons / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology*; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology*; D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods; D038524:Diffusion Magnetic Resonance Imaging; D020558:GTP Phosphohydrolases; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation; D009460:Neurologic Examination
D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human