Journal Article

Metabolic Signatures Differentiate Rett Syndrome From Unaffected Siblings

Glaze, Daniel G., Percy, Alan K., Lane, Jane, Heydemann, Peter, Annese, Fran, Skinner, Steven A., Kaufmann, Walter E., Neul, Jeffrey L., Jones, Mary

2020

Overview

Rett syndrome (RTT, OMIM 312750), a severe neurodevelopmental disorder characterized by regression with loss of spoken language and hand skills, development of characteristic hand stereotypies, and gait dysfunction, is primarily caused by mutations in the X-linked gene ( ). Currently, treatment options are limited to symptomatic management, however, reversal of disease phenotype is possible in mouse models by restoration of normal gene expression. A significant challenge is the lack of biomarkers of disease state, disease severity, or treatment response. Using a non-targeted metabolomic approach we evaluated metabolite profiles in plasma from thirty-four people with RTT compared to thirty-seven unaffected age- and gender-matched siblings. We identified sixty-six significantly altered metabolites that cluster broadly into amino acid, nitrogen handling, and exogenous substance pathways. RTT disease metabolite and metabolic pathways abnormalities point to evidence of oxidative stress, mitochondrial dysfunction, and alterations in gut microflora. These observed changes provide insight into underlying pathological mechanisms and the foundation for biomarker discovery of disease severity biomarkers.

• Publisher: Frontiers Research Foundation,Frontiers Media S.A
• Subject: Amino acids / Animal models / biomarker (development) / Biomarkers / Gait / Gene expression / Intestinal microflora / MeCP2 / MeCP2 protein / Metabolic pathways / Metabolites / Metabolomics / metabolomics (OMICS) / Methyl-CpG binding protein / Microbiota / Mitochondria / Mutation / Neurodevelopmental disorders / Neuroscience / Oxidative stress / Phenotypes / Rett syndrome / Siblings / urea cycle