| Title | Analyses of SLC13A5-epilepsy patients reveal perturbations of TCA cycle. |
| Publication Type | Journal Article |
| Year of Publication | 2017 |
| Authors | Bainbridge, MN, Cooney, E, Miller, M, Kennedy, AD, Wulff, JE, Donti, T, Jhangiani, SN, Gibbs, RA, Elsea, SH, Porter, BE, Graham, BH |
| Journal | Mol Genet Metab |
| Volume | 121 |
| Issue | 4 |
| Pagination | 314-319 |
| Date Published | 2017 08 |
| ISSN | 1096-7206 |
| Keywords | Child, Citric Acid, Citric Acid Cycle, Female, Humans, Infant, Newborn, Male, Mass Spectrometry, Metabolome, Metabolomics, Mutation, Mutation, Missense, Seizures, Spasms, Infantile, Symporters, Whole Exome Sequencing |
| Abstract | 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. |
| DOI | 10.1016/j.ymgme.2017.06.009 |
| Alternate Journal | Mol Genet Metab |
| PubMed ID | 28673551 |
| PubMed Central ID | PMC7539367 |
| Grant List | R01 GM098387 / GM / NIGMS NIH HHS / United States T32 GM007526 / GM / NIGMS NIH HHS / United States |