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

Metab Brain Dis. 2016 Jun;31(3):717-21. doi: 10.1007/s11011-016-9793-2. Epub 2016 Jan 16.

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: LTBL; Mitochondrial morphology; Mitochondrial translation; OXPHOS; ROS.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Lactic / diagnostic imaging
  • Acidosis, Lactic / genetics*
  • Agenesis of Corpus Callosum / diagnostic imaging
  • Agenesis of Corpus Callosum / genetics*
  • Brain / diagnostic imaging
  • Fatal Outcome
  • Glutamate-tRNA Ligase / genetics*
  • Humans
  • Hypoglycemia / diagnostic imaging
  • Hypoglycemia / genetics*
  • Infant, Newborn
  • Male
  • Mitochondrial Diseases / diagnostic imaging
  • Mitochondrial Diseases / genetics*
  • Recurrence
  • Ultrasonography

Substances

  • Glutamate-tRNA Ligase
  • glutamyl-tRNA synthetase 2, mitochondrial, human