title: [Clinical and molecular genetic diagnosis of leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation in children].
abstract: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a recently described disorder with autosomal recessive model of inheritance. Mutations in the DARS2 gene, which encode mitochondrial aspartyl-tRNA synthetase, have been found. We present 31 cases with characteristic clinical and neuroimaging findings of this disorder. Patients have been stratified into two groups (early and late forms) by age-at-onset and clinical symptoms. The early form was characterized clinically by progressive pyramidal dysfunction, cerebellar and intellectual problems appeared later. Patients with the late form had cerebellar and sensitive ataxia, disturbances of muscle tonus, spastic type, mostly in the low extremities, polyneuropathic and rarely - psychoorganic syndrome. The brain MRI of all patients was characterized by inhomogeneous T2W signal abnormalities in the periventricular and deep white matter and a strikingly selective involvement of certain brainstem and spinal tracts. Most of the patients were compound-heterozygous for common mutations in the DARS2. We found 4 new mutations associated with LBSL. This is the first clinical and molecular-genetic investigation of this rare leukoencephalopathy in Russia.
authors.forename: S V
authors.initials: SV
authors.lastname: Mikhaĭlova
authors.forename: E Iu
authors.initials: EIu
authors.lastname: Zakharova
authors.forename: A V
authors.initials: AV
authors.lastname: Banin
authors.forename: A A
authors.initials: AA
authors.lastname: Demushkina
authors.forename: A S
authors.initials: AS
authors.lastname: Petrukhin
mesh_terms: D001933:Brain Stem; D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods*; D003937:Diagnosis, Differential; D006801:Humans; D019344:Lactic Acid / Q000097:blood*; D056784:Leukoencephalopathies / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D013116:Spinal Cord
chemical_list: D019344:Lactic Acid