Analyses of SLC13A5-epilepsy patients reveal perturbations of TCA cycle

Matthew N. Bainbridge, Erin Cooney, Marcus Miller, Adam D. Kennedy, Jacob E. Wulff, Taraka Donti, Shalini N. Jhangiani, Richard A. Gibbs, Sarah H. Elsea, Brenda E. Porter, Brett H. Graham

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


Objective To interrogate the metabolic profile of five subjects from three families with rare, nonsense and missense mutations in SLC13A5 and Early Infantile Epileptic Encephalopathies (EIEE) characterized by severe, neonatal onset seizures, psychomotor retardation and global developmental delay. Methods Mass spectrometry of plasma, CSF and urine was used to identify consistently dysregulated analytes in our subjects. Results Distinctive elevations of citrate and dysregulation of citric acid cycle intermediates, supporting the hypothesis that loss of SLC13A5 function alters tricarboxylic acid cycle (TCA) metabolism and may disrupt metabolic compartmentation in the brain. Significance Our results indicate that analysis of plasma citrate and other TCA analytes in SLC13A5 deficient patients define a diagnostic metabolic signature that can aid in diagnosing children with this disease.

Original languageEnglish (US)
Pages (from-to)314-319
Number of pages6
JournalMolecular Genetics and Metabolism
Issue number4
StatePublished - Aug 2017
Externally publishedYes


  • Metabolomics
  • SLC13A5
  • Seizure
  • Tricarboxylic acid cycle

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology


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