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.
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Abbreviations
- LBSL:
-
Leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate
- MRI:
-
Magnetic resonance imaging
- MRS:
-
Magnetic resonance spectroscopy
References
Scheper GC, van der Klok T, van Andel RJ et al (2007) Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Nat Genet 39(4):534–539
Isohanni P, Linnankivi T, Buzkova J et al (2010) DARS2 mutations in mitochondrial leukoencephalopathy and multiple sclerosis. J Med Genet 47(1):66–70
Labauge P, Dorboz I, Eymard-Pierre E et al (2011) Clinically asymptomatic adult patient with extensive LBSL MRI pattern and DARS2 mutations. J Neurol 258(2):335–337
Lin J, Chiconelli Faria E, Da Rocha AJ et al (2010) Leukoencephalopathy with brainstem and spinal cord involvement and normal lactate: a new mutation in the DARS2 gene. J Child Neurol 25(11):1425–1428
Linnankivi T, Lundbom N, Autti T et al (2004) Five new cases of a recently described leukoencephalopathy with high brain lactate. Neurology 63(4):688–692
Mierzewska H, van der Knaap MS, Scheper GC et al (2011) Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation in the first Polish patient. Brain Dev
Petzold GC, Bohner G, Klingebiel R et al (2006) Adult-onset leucoencephalopathy with brain stem and spinal cord involvement and normal lactate. J Neurol Neurosurg Psychiatry 77(7):889–891
Serkov SV, Pronin IN, Bykova OV et al (2004) Five patients with a recently described novel leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate. Neuropediatrics 35(1):1–5
Tavora DG, Nakayama M, Gama RL et al (2007) Leukoencephalopathy with brainstem and spinal cord involvement and high brain lactate: report of three Brazilian patients. Arq Neuropsiquiatr 65(2B):506–511
Uluc K, Baskan O, Yildirim KA et al (2008) Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case with distinct MRI findings. J Neurol Sci 273(1–2):118–122
van der Knaap MS, van der Voorn P, Barkhof F et al (2003) A new leukoencephalopathy with brainstem and spinal cord involvement and high lactate. Ann Neurol 53(2):252–258
Sharma S, Sankhyan N, Kumar A et al (2011) Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case without elevated white matter lactate. J Child Neurol 26(6):773–776
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Tzoulis, C., Tran, G.T., Gjerde, I.O. et al. Leukoencephalopathy with brainstem and spinal cord involvement caused by a novel mutation in the DARS2 gene. J Neurol 259, 292–296 (2012). https://doi.org/10.1007/s00415-011-6176-9
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DOI: https://doi.org/10.1007/s00415-011-6176-9