Abstract
Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) is a hereditary disorder caused by biallelic variants in the EARS2 gene. Patients exhibit developmental delay, hypotonia, and hyperreflexia. Brain magnetic resonance imaging (MRI) reveals T2-hyperintensities in the deep white matter, thalamus, and brainstem, which generally stabilize over time. Herein, we report a case of LTBL, showing remitting and exacerbating white matter lesions. A non-consanguineous Japanese boy exhibited unsteady head control with prominent hypotonia, with no family history of neurological diseases. Brain MRI at one year of age revealed extensive T2-hyperintensities on the cerebral white matter, cerebellum, thalamus, basal ganglia, pons, and medulla oblongata. Magnetic resonance spectroscopy of the lesions showed lactate and myoinositol peaks. Whole-exome sequencing yielded novel compound heterozygous EARS2 variants of c.164G>T, p.Arg55Leu and c.484C>T, p.Arg162Trp. Interestingly, the lesions were reduced at three years of age, and new lesions emerged at eight years of age. At 10 years of age, the lesions were changed in the corpus callosum, deep cerebral white matter, and cerebellum, without physical exacerbation. The les...Continue Reading
References
Mar 2, 1986·Nature·H Bedouelle, G Winter
Jul 6, 2010·Nucleic Acids Research·Osamu NurekiRyuichiro Ishitani
Oct 26, 2011·The Biochemical Journal·Laura van BergeGert C Scheper
Apr 12, 2012·Brain : a Journal of Neurology·Marjan E SteenwegMassimo Zeviani
Sep 26, 2012·Brain : a Journal of Neurology·Beril TalimRita Horvath
Jul 25, 2014·JAMA : the Journal of the American Medical Association·Robert W TaylorPatrick F Chinnery
Apr 10, 2015·JIMD Reports·Roberta BiancheriClaudio Bruno
May 9, 2015·Science·UNKNOWN GTEx Consortium
Jan 8, 2016·PLoS Genetics·Masakazu KohdaYasushi Okazaki
Jan 19, 2016·Metabolic Brain Disease·Katharina DanhauserFelix Distelmaier
Feb 20, 2016·Journal of Child Neurology·Birce Dilge TaskinPhillip Lawrence Pearl
Apr 28, 2016·Brain & Development·Olcay GüngörKürşad Aydın
May 22, 2016·Journal of the Neurological Sciences·Sevim ŞahinGülden Yorgancıoğlu Budak
Jun 13, 2016·Journal of Translational Medicine·Ewa PronickaRafał Płoski
Aug 31, 2016·JIMD Reports·Renata OliveiraRobert W Taylor
Nov 12, 2016·Frontiers in Neuroanatomy·Susan J LindsayPatrick F Chinnery
Jun 22, 2017·Human Molecular Genetics·Rebecca Meyer-Schuman, Anthony Antonellis
Jul 28, 2017·Neurology. Genetics·Nathan McNeillDaniele Ghezzi
May 23, 2018·Nucleic Acids Research·Andrew WaterhouseTorsten Schwede
Sep 15, 2019·Journal of the Neurological Sciences·Pankaj PrasunBryn D Webb
Dec 17, 2019·Journal of Neurodevelopmental Disorders·Amena Smith FineAli Fatemi
Jul 30, 2020·Scientific Reports·Florian KaiserMichael Schroeder