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Metabolic Brain Disease

, Volume 31, Issue 3, pp 717–721 | Cite as

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

  • Katharina Danhauser
  • Tobias B. Haack
  • Bader Alhaddad
  • Marlen Melcher
  • Annette Seibt
  • Tim M. Strom
  • Thomas Meitinger
  • Dirk Klee
  • Ertan Mayatepek
  • Holger ProkischEmail author
  • Felix DistelmaierEmail author
Short Communication

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.

Keywords

OXPHOS LTBL ROS Mitochondrial translation Mitochondrial morphology 

Notes

Compliance with ethical standards

Funding

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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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Katharina Danhauser
    • 1
  • Tobias B. Haack
    • 2
    • 3
  • Bader Alhaddad
    • 2
    • 3
  • Marlen Melcher
    • 1
  • Annette Seibt
    • 1
  • Tim M. Strom
    • 2
    • 3
  • Thomas Meitinger
    • 2
    • 3
    • 4
  • Dirk Klee
    • 5
  • Ertan Mayatepek
    • 1
  • Holger Prokisch
    • 2
    • 3
    Email author
  • Felix Distelmaier
    • 1
    Email author
  1. 1.Department of General Pediatrics, Neonatology and Pediatric CardiologyUniversity Children’s Hospital, Heinrich-Heine-University DüsseldorfDüsseldorfGermany
  2. 2.Institute of Human GeneticsTechnische Universität MünchenMunichGermany
  3. 3.Institute of Human GeneticsHelmholtz Zentrum MünchenNeuherbergGermany
  4. 4.Munich Cluster for Systems Neurology (SyNergy)MunichGermany
  5. 5.Medical Faculty, Department of Diagnostic and Interventional RadiologyUniversity DüsseldorfDüsseldorfGermany

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