Clinical Cases of Leukoencephalopathy with Predominant Lesion of the Brain Stem, Spinal Cord and High Blood Lactate in the MR Spectroscopy (Mitochondrial Aspartyl-tRNASynthetase Deficiency)
https://doi.org/10.15690/vsp.v14i6.1483
Abstract
Leukoencephalopathy with predominant lesion of the brain stem, spinal cord and high blood lactate in the MR spectroscopy is a hereditary disease characterized by slowly progressing cerebellar, pyramidal disorders, disorders involving the lesion of posterior columns of the spinal cord and highly specific changes according to the data of MRI and magnetic resonanse spectroscopy of the brain and spinal cord. This disease is one of nuclear inherited mitochondrial encephalomyopathies, caused by mutations in the DARS2 gene and characterized by mitochondrial aspartyl-tRNA-synthetase deficiency. This article presents the record of the disease description, its genetic basis, clinical features and diagnostic criteria. The article describes two clinical cases of the disease in 9-year and 17-year old girls.
About the Authors
Ye. P. Kolesnikova
Scientific Centre of Children Health, Moscow, Russian Federation
Russian Federation
Russian Federation
L. M. Kuzenkova
Scientific Centre of Children Health, Moscow, Russian Federation
Sechenov First Moscow State Medical University, Moscow, Russian Federation
Russian Federation
Russian Federation
K. V. Savostyanov
Scientific Centre of Children Health, Moscow, Russian Federation
Russian Federation
Russian Federation
O. V. Globa
Scientific Centre of Children Health, Moscow, Russian Federation
Russian Federation
Russian Federation
T. V. Podkletnova
Scientific Centre of Children Health, Moscow, Russian Federation
Russian Federation
Russian Federation
References
1. Lee-Jun C. Wong. Mitochondrial Syndromes with Leukoencephalopathies. Semin neurol. 2012;32(1):55–61.
2. Globa O, Sorokina E, Zhourkova N, Kondakova O, Tikchomirov E, Semenova N, Basargina E, Bykova O, Kuzenkova L, Pinelis V. Mitochondrial disorders in children. Acta Paediatrica. 2008;97(1).
3. Lebre AS, Rio M, Faivre d'Arcier L, Vernerey D, Landrieu P, Slama A, Jardel C, Laforet P, Rodriguez D, Dorison N, Galanaud D, Chabrol B, Paquis-Flucklinger V, Grevent D, Edvardson S, Steffann J, Funalot B, Villeneuve N, Valayannopoulos V, de Lonlay P, Desguerre I, Brunelle F, Bonnefont JP, Rotig A, Munnich A,Boddaert N. A common pattern of brain MRI imaging in mitochondrial diseases with complex I deficiency. J Med Genet. 2011;48(1):16–23.
4. Lerman-Sagie T, Leshinsky-Silver E, Watemberg N, Luckman Y, Lev D. White matter involvement in mitochondrial diseases. Mol Genet Metab. 2005;84(2):127–136.
5. Глоба ОВ, Кузенкова ЛМ, Андреенко НВ, Журкова НВ, Кондакова ОБ. Нейрофизиологические и нейровизуализационные особенности детей с митохондриальной патологией. Сб. материалов XVI Съезда педиатров России «Актуальные проблемы педиатрии». М. 2009. С. 87.
6. Михайлова СВ, Захарова ЕЮ, Банин АВ, Дёмушкина АА, Петрухин АС. Клинические проявления и молекулярно-генетическая диагностика лейкоэнцефалопатии с преимущественным поражением ствола мозга, спинного мозга и повышенным лактатом у детей. Клиника нервных и психических заболеваний. 2009;9:16–22.
7. Scheper GC, van der Klik T, an Andel RJ, van Berkel CG, Sissler M, Smet J, Muravina TI, Serkov SV, Uziel G, Bugiani M, Schiffmann R, Krageloh-Mann I, Smeitink JA, Florentz C, van Coster R, Pronk JC, van der Knaap MS. Mitochondrial aspartyl tRNA syntethase deficiency causes leucoencephalopathy with brain stem and spinal cord invelvment and lactate evaluation. Nature Genet. 2007;39:534–539.
8. Атлас редких болезней. Под ред. А.А. Баранова, Л.С. Намазовой-Барановой. М. 2013. 303 с.
9. Knaap van der MS, Voorn van der P, Barkhof F, Van Coster R, Krageloh-Mann I, Feigenbaum A, Blaser S, Vles JS, Rieckmann P, Pouwels PJ. A new leukoencephalopathy with brainstem and spinal cord involvment and high lactate. AnnNeurol. 2003;53:252–258.
10. Гузева ВИ, Ефет ЕА, Николаева ОМ. Лейкоэнцефалопатия с преимущественным поражением ствола мозга, спинного мозга и повышенным лактатом при МР-спектроскопии (клиническое наблюдение). Нейрохирургия и неврология детского возраста. 2012;1(13):16–22.
11. Bergevan L, Dooves S, Berkelvan CG, Polder E, Knaapvander MS, Scheper GC. Leucoencephalopathy with brain steam and spinal cord involvment and lactate evaluation is associated with cell type dependent splicing of mtAspRS mRNA. Biochem J. 2012; 441(3):955–962.
12. Berge van L, Hamilton BM, Linnankivi T, Uziel G, Steenweg ME, Isohanni P, Wolf NI, Krageloh-Mann I, Brautaset NJ, Andrews I, Jong de BA, Ghamdi al M, Wieringen van WN, Tannous BA, Hulleman E, Wurdinger T, Berkel van CGM, Polder E, Abbink TEM., Struys EA,
13. Scheper GS, Knaap van der MS. Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation: clinical and genetic characterization and target for therapy. Brain. 2014;137:1019–1029.
14. Synofzik M, Schicks J, Lindig T, Biskup S, Schidt T, Hansel J, Lehmann-Horn F, Schols L. Acetazolamide responsive exercise induced epizodic ataxia associated with a novel homozygous DARS2 mutation. J Med Genet. 2011;48(10):713–715.
15. Steenweg ME, van Berge L, van Berkel CG, de Coo IF, Temple IK, Brockmann K, Mendonca CI, Vojta S, Kolk A, Peck D, Carr L, Uziel G, Feigenbaum A, Blaser S, Scheper GC, van der Knaap MS. Early onset LBSL: how severe does it get? Neuropediatrics. 2012;43(6):332–338.
16. Isohanni P, Linnankivi T, Buzkova J, Lonnqvist T, Pihko H, Valanne L, Tienari PJ, Elovaara I, Pirttila T, Reunanen M, Koivisto K, Marja vaara S, Suomalainen A. DARS2 mutation in mitochondrial leucoencephalo pathy and multiple sclerosis. J Med Genet. 2010;47:66–70.
17. Серков СВ, Пронин ИН, Фалеева ЛМ, Корниенко ВН. Нейрорентгенологические проявления лейкоэнцефалопатии с поражением ствола мозга, спинного мозга и повышенным лактатом (ЛСС-Л) в российской популяции. Результаты динамического исследования. Медицинская визуализация. 2004;4:113–121.
18. Steenweg ME, Pouwels PJ, Wolf NI, van Wieringen WN, Barkhof F, van der Knaap MS. Leucoencephalopathy with brainstem and spinal cord involvment and high lactate: quantitativa magnetic resonance imaging. Brain. 2011;134:3333–3341.
19. Tavora DG, Nakayama M, Gama RL, Alvim TC, Portugal D, Comerlato EA. Leukoencephalopathy with brainstem and spinal cord involvement and high brain lactate: report of three Brazilian patients. Arq Neuropsiquiatr. 2007;65(2B):506–511.
20. Uluc K, Baskan O, Yildirim KA, Ozsahin S, Koseoglu M, Isak B, Scheper GC, Gunal DI, van der Knaap MS. Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case with distinct MRI findings. J Neurol Sci. 2008;273:118–122.
21. Altintas A, Petek B, Isik N, Terzi M, Bolukbasi F, Tavsanli M, Saip S, Boz C, Aydin T, Arici-Duz O, Ozer F, Siva A. Clinical and radiological characteristics of tumefactive demyelinating lesions: follow up study. Mult Scler. 2012;18(10):1448–1453.
22. McAdam LC, Blaser SI, Banwell BL. Pediatric tumefactive demyelination: case series and review of the literature. Pediatr Neurol. 2002;26(1):18–25.
Review
For citations:
Kolesnikova Ye.P., Kuzenkova L.M., Savostyanov K.V., Globa O.V., Podkletnova T.V. Clinical Cases of Leukoencephalopathy with Predominant Lesion of the Brain Stem, Spinal Cord and High Blood Lactate in the MR Spectroscopy (Mitochondrial Aspartyl-tRNASynthetase Deficiency). Current Pediatrics. 2015;14(6):724-731. (In Russ.) https://doi.org/10.15690/vsp.v14i6.1483
Views:
2298
Email this article 
