Late-onset leukoencephalopathy with predominant damage to the brain stem, spinal cord and increased lactate (clinical observations)

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Abstract

Leukoencephalopathy with brain stem and spinal cord involvement and elevated lactate on magnetic resonance spectroscopy is a progressive hereditary disease of the nervous system clinically characterized by pyramidal and cerebellar dysfunction, dorsal column signs and sometimes axonal neuropathy with specific neuroimaging signs of damage to the nervous system, detected by magnetic resonance imaging. This disease is caused by mutations in the DARS2 gene. The article presents an analysis of three clinical cases with the manifestation of neurological symptoms in adolescence. Clinical features and magnetic resonance imaging findings are discussed, difficulties of differential diagnosis with multiple sclerosis are presented. Genetic screening algorithms are proposed.

About the authors

M. I. Karpova

South Ural State Medical University, Ministry of Health of Russia

Author for correspondence.
Email: kmi_2008@mail.ru
ORCID iD: 0000-0002-7653-3677

64 Vorovskogo St., Chelyabinsk 454092

Russian Federation

A. F. Vasilenko

South Ural State Medical University, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0001-5799-7233

64 Vorovskogo St., Chelyabinsk 454092

Russian Federation

D. G. Korotkova

South Ural State Medical University, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-0875-1963

64 Vorovskogo St., Chelyabinsk 454092

Russian Federation

I. V. Kochetkov

South Ural State Medical University, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0003-3169-9777

64 Vorovskogo St., Chelyabinsk 454092

Russian Federation

M. V. Shestakova

South Ural State Medical University, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-8955-1604
64 Vorovskogo St., Chelyabinsk 454092 Russian Federation

G. V. Buyanova

Chelyabinsk Regional Children’s Clinical Hospital

Email: fake@neicon.ru
ORCID iD: 0000-0002-9572-4647

42a Blyukhera St., Chelyabinsk 454087

Russian Federation

Z. Z. Zaripova

Chelyabinsk Regional Clinical Hospital

Email: fake@neicon.ru
ORCID iD: 0000-0001-8419-9026

70 Vorovskogo St.,Chelyabinsk, 454076

Russian Federation

References

  1. . Van der Knaap M.S., van der Voom P., Barkhof F. et al. A new leukoencephalopathy with brainstem and spinal cord involvement and high lactate. Ann Neurology 2003;53:252-8. doi: 10.1002/ana.10456. PMID: 24566671.
  2. Mikhaylova S.V., Zakharova E.L., Banin A.V. et al. Clinical manifestations and molecular genetic diagnosis of leukoencephalopathy with predominant damage to the brain stem, spinal cord and increased lactate in children. Journal of Neurology and Psychiatry named S.S. Korsakov = Zhurnal nevro-logii i psikhiatrii im. S.S. Korsakova 2009;109(9):16-22. (In Russ.).
  3. Steenweg M.E., van Berge L., van Berkel C.G. et al. Early-onset LBSL: how severe does it get? Neuropediatrics 2012;43:332-8. doi: 10.1055/s-0032-1329395. PMID: 23065766.
  4. Van Berge L., Hamilton E.M., Linnankivi T. et al. Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation: clinical and genetic characterization and target for therapy. Brain 2014;137:1019-29. doi: 10.1093/brain/awu026. PMID: 24566671.
  5. Huang Q.H., Xiao J.X., Wang J.M. et al. Clinical and genetic analysis of a family with leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Zhonghua Er Ke Za Zhi 2012;50(1):50—5. PMID: 22456076.
  6. Moore S.A., Kumar N., Gavrilova R.H. Leukoencephalopathy with brain stem and spinal cord involvement (and high lactate): raising the bar for diagnosis. J Neurol 2012;259(11):2494-7. doi: 10.1007/s00415-012-6596-1.
  7. Scheper G.C., van der Klok T., van Andel R.J. et al. Mitochondrial aspar-tyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Nat Genet 2007;39:534-9. doi: 10.1038/ng2013. PMID: 17384640.
  8. Van Berge L., Dooves S., van Berkel C.G. et al. Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation is associated with cell-type-dependent splicing of mtAspRS mRNA. Biochem J 2012;441(3):955-62. doi: 10.1042/BJ20110795. PMID: 22023289.
  9. Mikhaylova S.V., Zakharova E.Yu., Petrukhin A.S. Neurometabolic diseases in children and adolescents. Diagnosis and treatment approaches. M.: Litterra, 2011. 331 p. (In Russ.).
  10. Tavora D.G., Nakayama M., Gama R.L. et al. Leukoencephalopathy with brainstem and spinal cord involvement and high brain lactate: report of three Brazilian patients. Arq Neuropsiquiat 2007;65:506-11.
  11. Van der Knaap M.S., Valk J. Magnetic resonance of myelination and myelin disorders. Berlin: Springer Verlag, 2005. 1084 p.
  12. Alibas H., Koytak P.K., Ekinci G., Uluc K. A case with leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate (LBSL) with Its Characteristic Clinical and Neuroimaging Findings. Clin Neuroradiol 2014;24(3): 297-300. doi: 10.1007/s00062-013-0250-x. PMID: 24005482.
  13. Uluc K., Baskan O., Yildirim K.A. et al. Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case with distinct MRI findings. J Neurol Sci 2008;273:118-22. doi: 10.1016/j.jns.2008.06.002. PMID: 18619624.
  14. Bonnefond L., Fender A., Rudinger-Thirion J. et al. Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS. Biochemistry 2005;44(480):5-16. doi: 10.1021/bi047527z. PMID: 15779907.
  15. Biesecker L.G., Green R.C. Diagnostic clinical genome and exome sequencing. N Engl J Med 2014;370(25):2418—25. doi: 10.1056/NEJMra1312543. PMID: 25229935.
  16. Moroz A.A., Nuzhnjy E.P., Seliverstov Yu.A. et al. A rare form of enceph gene associated blades DARS2. Nevrologicheskiy zhur-nal = Neurological journal 2018;23(2):71—7. (In Russ.).
  17. Moroz A.A. Hereditary diseases of the nervous system in adults associated with pathology of the white matter of the brain: dis. ... cand. med. sciences. Moscow: FGBNU Scientific Center of Neurology, 2018. (In Russ.).

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Copyright (c) 2019 Karpova M.I., Vasilenko A.F., Korotkova D.G., Kochetkov I.V., Shestakova M.V., Buyanova G.V., Zaripova Z.Z.

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