N8-acetylspermidine as a potential plasma biomarker for Snyder-Robinson syndrome identified by clinical metabolomics
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Clinical metabolomics has emerged as a powerful tool to study human metabolism in health and disease. Comparative statistical analysis of untargeted metabolic profiles can reveal perturbations of metabolite levels in diseases and thus has the potential to identify novel biomarkers. Here we have applied a simultaneous genetic-metabolomic approach in twin boys with epileptic encephalopathy of unclear etiology. Clinical exome sequencing identified a novel missense mutation in the spermine synthase gene (SMS) that causes Snyder-Robinson syndrome (SRS). Untargeted plasma metabolome analysis revealed significantly elevated levels of N8-acetylspermidine, a precursor derivative of spermine biosynthesis, as a potential novel plasma biomarker for SRS. This result was verified in a third patient with genetically confirmed SRS. This study illustrates the potential of metabolomics as a translational technique to support exome data on a functional and clinical level.
KeywordsSpermine Spermidine Myoclonic Jerk HFBA Clinical Exome Sequencing
We thank Annegret Flier and Joern Oliver Sass for establishing lymphoblast cultures of the twin patients.
Compliance with ethic guidelines
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000.
Conflict of interests
Consent was obtained from all patients or their legal guardians for being included in the study.