Multi-Omic integration after carbon monoxide toxicity in a child reveals gene transcripts related to Parkinson and Multiple Sclerosis

Abstract

Background This report highlights the unique transcriptomic and lipidomic changes noted in a 4-year-old African American female patient exposed to a house fire. She required admission to the pediatric Intensive care unit due to organ failure that resulted from CO and cyanide toxicity. Patient was neurologically intact initially but later developed neurological symptoms consistent with Parkinsonism, a transient state resembling Parkinson’s Disease. Results An integrative omics-based approach was used to examine both gene expression and the lipidome of the patient which was then compared to 4 control patients. Total blood RNA from a PaxGene®collection system was correlated to plasma-based metabolomics measured over three time points and correlated with the clinical condition of the patient. We see significant elevation of the Parkinson’s associated gene ( SELENOT ) on day one. This gene plays a crucial role in the protection of dopaminergic neurons against oxidative stress in Parkinson's disease. The Multiple Sclerosis linked gene DDX39B which mediates ATP hydrolysis during pre-mRNA splicing was increased on day 8. We noted increased UGCG gene expression which correlated with increased ceramide lipids on lipidome analysis. The elevated ratio of hexosylceramide to its ceramide precursor is indicative of an elevated UGCG mediated ceramide glucosyltransferase activity. This correlation of clinical symptoms with both increased gene activity and lipid dyshomeostasis is unique, highlighting the potential of personalized omics. ConclusionsIn clinical practice, the ability to predict and quantify neurological injury using gene expression has the potential to make meaningful changes to management. This report shows the potential for real time transcriptomics and metabolomics to modify not only initial therapy, but the eventual physical rehabilitation of patients exposed to neurotoxins.