Abstract
Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) is a novel mitochondrial disease caused by mutations in EARS2, which encodes the mitochondrial glutamyl-tRNA synthetase (mtGluRS). A distinctive brain MRI pattern is the hallmark of the disease.
A 6-year-old boy presented at 3 months with feeding difficulties and muscle hypotonia. Brain MRI, at 8 months, showed hyperintensity of the deep cerebral and cerebellar white matter, thalamus, basal ganglia, brainstem, and thin corpus callosum. From the second year of life onward, the child reported global clinical improvement, parallel to partial resolution of brain MRI pattern. However, the last neuroimaging assessment revealed novel lesions within the left caudate and pallidum nuclei. DNA genomic sequencing analysis identified a novel EARS2 mutation.
This case expands the clinical and neuroradiological phenotype of LTBL presenting intermediate clinical manifestations between the severe and milder forms of the disease and previously unreported brain MRI features.
Competing interests: None declared
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Acknowledgments
We wish to thank Paolo Broda and Annagloria Incontrera for technical assistance.
The financial supports of Telethon Italy (Grant no. GUP09004) and of Pierfranco and Luisa Mariani Foundation, Italy, are gratefully acknowledged.
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Communicated by: Nicole Wolf, MD PhD
Appendices
Take-Home Message
In this report, we present the first long-term clinical and neuroradiological follow-up of a LTBL/EARS2 patient, showing previously unreported brain MRI features.
Compliance with Ethics Guidelines
Roberta Biancheri, Eleonora Lamantea, Mariasavina Severino, Daria Diodato, Marina Pedemonte, Denise Cassandrini, Alexandra Ploederl, Federica Trucco, Chiara Fiorillo, Carlo Minetti, Filippo M. Santorelli, Massimo Zeviani, and Claudio Bruno declare that they have no conflict of interest.
Informed Consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
Author Contributions
Study concept and design: Biancheri and Bruno
Acquisition of data: Biancheri, Lamantea, Severino Diodato, Cassandrini, Pedemonte, Trucco, Fiorillo, Ploederl, and Bruno
Analysis and interpretation of data: Biancheri, Lamantea, Santorelli, Zeviani, and Bruno
Drafting of the manuscript: Biancheri, Zeviani, and Bruno
Critical revision of the manuscript for important intellectual content: Minetti, Santorelli, Zeviani, and Bruno
Obtained funding: Zeviani
Administrative, technical, and material support: Bruno
Study supervision: Biancheri, Lamantea, and Bruno
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Biancheri, R. et al. (2015). Expanding the Clinical and Magnetic Resonance Spectrum of Leukoencephalopathy with Thalamus and Brainstem Involvement and High Lactate (LTBL) in a Patient Harboring a Novel EARS2 Mutation. In: Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters, V. (eds) JIMD Reports, Volume 23. JIMD Reports, vol 23. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_434
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DOI: https://doi.org/10.1007/8904_2015_434
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