title: Leukoencephalopathy with brainstem and spinal cord involvement caused by a novel mutation in the DARS2 gene.
abstract: Leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate (LBSL) is a rare, autosomal recessive disorder caused by mutations in the gene encoding a mitochondrial aspartyl-tRNA synthetase, DARS2. The disease is characterized by progressive spastic ataxia and magnetic resonance imaging (MRI) shows a highly characteristic leukoencephalopathy with multiple long tract involvement. We describe the clinical and radiological features of two new cases of LBSL and report a novel pathogenic mutation in the DARS2 gene. Both patients had typical clinical and radiological findings, although no elevated lactate was found. The severity of MRI changes did not correlate with clinical course and severity suggesting that, although of highly specific diagnostic value, MRI does not necessarily reflect clinical activity and should not be used to assess disease severity or prognosis in LBSL.
authors.affiliation: Department of Neurology, Haukeland University Hospital, 5021, Bergen, Norway. chtzoulis@yahoo.com
authors.forename: Charalampos
authors.initials: C
authors.lastname: Tzoulis
authors.forename: Gia Tuong
authors.initials: GT
authors.lastname: Tran
authors.forename: Ivar Otto
authors.initials: IO
authors.lastname: Gjerde
authors.forename: Jan
authors.initials: J
authors.lastname: Aasly
authors.forename: Gesche
authors.initials: G
authors.lastname: Neckelmann
authors.forename: Jana
authors.initials: J
authors.lastname: Rydland
authors.forename: Viktoria
authors.initials: V
authors.lastname: Varga
authors.forename: Pia
authors.initials: P
authors.lastname: Wadel-Andersen
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Bindoff
mesh_terms: D000328:Adult; D017668:Age of Onset; D001226:Aspartate-tRNA Ligase / Q000235:genetics*; D001933:Brain Stem / Q000473:pathology*; D002648:Child; D005260:Female; D006801:Humans; D056784:Leukoencephalopathies / Q000235:genetics* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009154:Mutation; D035781:Siblings; D013116:Spinal Cord / Q000473:pathology*
chemical_list: D001226:Aspartate-tRNA Ligase; C558608:DARS2 protein, human