title: Absent Thalami Caused by a Homozygous EARS2 Mutation: Expanding Disease Spectrum of LTBL.
abstract: Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) is caused by autosomal recessive EARS2 mutations. Onset is most often in infancy, but in severe cases in the neonatal period. Patients typically have magnetic resonance imaging (MRI) signal abnormalities involving the thalamus, brainstem, and deep cerebral white matter. Most signal abnormalities resolve, but in severe cases at the expense of tissue loss. Here, we report a patient with an encephalopathy of antenatal onset. His early MRI at 8 months of age showed signal abnormalities in the deep cerebral white matter that improved over time. The thalami were absent with the configuration of a developmental anomaly, without evidence of a lesion. We hypothesized that this was a case of LTBL in which the thalamic damage occurred antenatally and was incorporated in the normal brain development. The diagnosis was confirmed by a novel homozygous EARS2 mutation. Our case adds to the phenotypic and genetic spectrum of LTBL.
authors.affiliation: Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Sietske H
authors.initials: SH
authors.lastname: Kevelam
authors.affiliation: Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Femke C C
authors.initials: FC
authors.lastname: Klouwer
authors.affiliation: Department of Pediatric Neurology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Fock
authors.affiliation: Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: Gajja S
authors.initials: GS
authors.lastname: Salomons
authors.affiliation: Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marianna
authors.initials: M
authors.lastname: Bugiani
authors.affiliation: Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marjo S
authors.initials: MS
authors.lastname: van der Knaap
mesh_terms: D000293:Adolescent; D001933:Brain Stem / Q000378:metabolism; D005975:Glutamate-tRNA Ligase / Q000235:genetics*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D056784:Leukoencephalopathies / Q000235:genetics* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D013788:Thalamus / Q000473:pathology*
chemical_list: D019344:Lactic Acid; D005975:Glutamate-tRNA Ligase