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01-06-2016 | Short Communication

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

Authors: Katharina Danhauser, Tobias B. Haack, Bader Alhaddad, Marlen Melcher, Annette Seibt, Tim M. Strom, Thomas Meitinger, Dirk Klee, Ertan Mayatepek, Holger Prokisch, Felix Distelmaier

Published in: Metabolic Brain Disease | Issue 3/2016

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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Title: EARS2 mutations cause fatal neonatal lactic acidosis, recurrent hypoglycemia and agenesis of corpus callosum
Authors: Katharina Danhauser
Tobias B. Haack
Bader Alhaddad
Marlen Melcher
Annette Seibt
Tim M. Strom
Thomas Meitinger
Dirk Klee
Ertan Mayatepek
Holger Prokisch
Felix Distelmaier
Publication date: 01-06-2016
Publisher: Springer US
Published in: Metabolic Brain Disease / Issue 3/2016
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-016-9793-2

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

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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