Post-mortem tissue analyses in a patient with succinic semialdehyde dehydrogenase deficiency (SSADHD). I. Metabolomic outcomes

Trevor Kirby, Dana C. Walters, Madalyn Brown, Erwin Jansen, Gajja S. Salomons, Coleman Turgeon, Piero Rinaldo, Erland Arning, Paula Ashcraft, Teodoro Bottiglieri, Jean Baptiste Roullet, K. Michael Gibson

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14 Citations (Scopus)


Metabolomic characterization of post-mortem tissues (frontal and parietal cortices, pons, cerebellum, hippocampus, cerebral cortex, liver and kidney) derived from a 37 y.o. male patient with succinic semialdehyde dehydrogenase deficiency (SSADHD) was performed in conjunction with four parallel series of control tissues. Amino acids, acylcarnitines, guanidino- species (guanidinoacetic acid, creatine, creatinine) and GABA-related intermediates were quantified using UPLC and mass spectrometric methods that included isotopically labeled internal standards. Amino acid analyses revealed significant elevation of aspartic acid and depletion of glutamine in patient tissues. Evidence for disruption of short-chain fatty acid metabolism, manifest as altered C4OH, C5, C5:1, C5DC (dicarboxylic) and C12OH carnitines, was observed. Creatine and guanidinoacetic acids were decreased and elevated, respectively. GABA-associated metabolites (total GABA, γ-hydroxybutyric acid, succinic semialdehyde, 4-guanidinobutyrate, 4,5-dihydroxyhexanoic acid and homocarnosine) were significantly increased in patient tissues, including liver and kidney. The data support disruption of fat, creatine and amino acid metabolism as a component of the pathophysiology of SSADHD, and underscore the observation that metabolites measured in patient physiological fluids provide an unreliable reflection of brain metabolism.

Original languageEnglish
Pages (from-to)601-614
Number of pages14
JournalMetabolic brain disease
Issue number4
Early online date2020
Publication statusPublished - 1 Apr 2020


  • Acylcarnitines
  • Amino acids
  • GABA
  • Metabolomics
  • γ-Hydroxybutyric acid

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