Publications

BACKGROUND AND AIMS: Hirschsprung disease (HSCR) is a congenital disorder of unknown etiology affecting the enteric nervous system (ENS). Since the early  gestational development of the ENS is dependent on the prenatal maternal  metabolic environment, the objective of this pilot study was to explore the role  of specific maternal plasma metabolites in the etiology of HSCR. METHODS: In this  cross-sectional study, postnatal (as a surrogate for prenatal) plasma samples  were obtained from mothers of children diagnosed with HSCR (n = 7) and  age-matched mothers of normal children (n = 6). The plasma metabolome was  analyzed by ultra-high-pressure liquid chromatography and mass spectrometry.  Metabolites were identified by mzCloud using Compound Discoverer software. Using  an untargeted metabolomics workflow, metabolites with case versus control group  differences were identified. RESULTS: A total of 268 unique plasma metabolites  were identified and annotated in maternal plasma. Of these, 57 were significantly  different between case and control groups (P < 0.05, t-test). Using a false  discovery rate corrected cutoff of 10% to adjust for multiple comparisons, 19  metabolites were significantly different in HSCR cases, including carnitines,  medium-chain fatty acids, and glutamic acid. Pathways affected were for amino  acid and lipid metabolism. CONCLUSION: Disordered prenatal metabolic pathways may  be involved in the etiopathogenesis of HSCR in the developing fetus. This is the  first study to assess maternal plasma metabolomics in HSCR.