2. Academic Validation
  3. Global Metabolomics Discovers Two Novel Biomarkers in Pyridoxine-Dependent Epilepsy Caused by ALDH7A1 Deficiency

Global Metabolomics Discovers Two Novel Biomarkers in Pyridoxine-Dependent Epilepsy Caused by ALDH7A1 Deficiency

  • Int J Mol Sci. 2022 Dec 16;23(24):16061. doi: 10.3390/ijms232416061.
Hans-Otto Böhm 1,  Mazyar Yazdani 1,  Elise Mørk Sandås 1,  Anja Østeby Vassli 1,  Erle Kristensen 1,  Helge Rootwelt 1,  Hanne Bendiksen Skogvold 1 2,  Eylert Brodtkorb 3 4,  Katja Benedikte Prestø Elgstøen 1
Affiliations

Affiliations

  • 1 Department of Medical Biochemistry, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway.
  • 2 Department of Mechanical, Electronic and Chemical Engineering, Faculty of Technology, Art and Design, Oslo Metropolitan University, Pilestredet 35, 0166 Oslo, Norway.
  • 3 Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
  • 4 Department of Neurology, St. Olav's Hospital, University Hospital, 7006 Trondheim, Norway.
PMID: 36555701 DOI: 10.3390/ijms232416061
Abstract

Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive developmental and epileptic encephalopathy caused by pathogenic variants in the ALDH7A1 gene (PDE-ALDH7A1), which mainly has its onset in neonates and infants. Early diagnosis and treatment are crucial to prevent severe neurological sequelae or death. Sensitive, specific, and stable biomarkers for diagnostic evaluations and follow-up examinations are essential to optimize outcomes. However, most of the known biomarkers for PDE lack these criteria. Additionally, there is little discussion regarding the interdependence of biomarkers in the PDE-ALDH7A1 metabolite profile. Therefore, the aim of this study was to understand the underlying mechanisms in PDE-ALDH7A1 and to discover new biomarkers in the plasma of patients using global metabolomics. Plasma samples from 9 patients with genetically confirmed PDE-ALDH7A1 and 22 carefully selected control individuals were analyzed by ultra high performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). Two novel and reliable pyridoxine-independent diagnostic markers, 6-hydroxy-2-aminocaproic acid (HACA) and an isomer of C9H11NO4, were identified. Furthermore, a possible reaction mechanism is proposed for HACA. This study demonstrates the capability of global metabolomics in disease screening to detect established and novel biomarkers.

Keywords

6-hydroxy-(S)-2-aminocaproic acid (HACA); ALDH7A1; C9H11NO4 isomer; UHPLC-HRMS; biomarker; global metabolomics; pyridoxine-dependent epilepsy.

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