EARS2 mutations cause fatal neonatal lactic acidosis, recurrent hypoglycemia and agenesis of corpus callosum.

Metabolic Brain Disease
Katharina DanhauserFelix Distelmaier

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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Citations

Aug 10, 2016·Metabolic Brain Disease·Fabian BaertlingFelix Distelmaier
Nov 1, 2016·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Fabian BaertlingFelix Distelmaier
Dec 17, 2019·Journal of Neurodevelopmental Disorders·Amena Smith FineAli Fatemi
Jul 28, 2017·Neurology. Genetics·Nathan McNeillDaniele Ghezzi
Jun 22, 2017·Human Molecular Genetics·Rebecca Meyer-Schuman, Anthony Antonellis
Apr 16, 2021·Journal of Inherited Metabolic Disease·Min NiRalph J DeBerardinis
May 12, 2021·Molecular Genetics and Metabolism·Charles-Joris RouxNathalie Boddaert

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