Abstract
Mitochondrial aminoacyl tRNA synthetases are essential for organelle protein synthesis. Genetic defects affecting the function of these enzymes may cause pediatric mitochondrial disease. Here, we report on a child with fatal neonatal lactic acidosis and recurrent hypoglycemia caused by mutations in EARS2, encoding mitochondrial glutamyl-tRNA synthetase 2. Brain ultrasound revealed agenesis of corpus callosum. Studies on patient-derived skin fibroblasts showed severely decreased EARS2 protein levels, elevated reactive oxygen species (ROS) production, and altered mitochondrial morphology. Our report further illustrates the clinical spectrum of the severe neonatal-onset form of EARS2 mutations. Moreover, in this case the live-cell parameters appeared to be more sensitive to mitochondrial dysfunction compared to standard diagnostics, which indicates the potential relevance of fibroblast studies in children with mitochondrial diseases.
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This project was supported by the BMBF funded German Network for Mitochondrial Disorders (mitoNET #01GM1113C) and by the E-Rare project GENOMIT (01GM1207). TBH was supported by the BMBF through the Juniorverbund in der Systemmedizin “mitOmics” (FKZ 01ZX1405C). KD was supported by a grant of the Forschungskommission of the Medical Faculty of the Heinrich-Heine-University Düsseldorf.
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Danhauser, K., Haack, T.B., Alhaddad, B. et al. EARS2 mutations cause fatal neonatal lactic acidosis, recurrent hypoglycemia and agenesis of corpus callosum. Metab Brain Dis 31, 717–721 (2016). https://doi.org/10.1007/s11011-016-9793-2
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DOI: https://doi.org/10.1007/s11011-016-9793-2