Metabolomic analysis of children with congenital heart disease complicated by neurological developmental abnormalities and CHD7 mutations

ObjectiveThis study aimed to characterize the clinical features and identify serum differential metabolites in children with left-to-right shunt congenital heart disease (CHD) complicated by neurodevelopmental abnormalities (NDA) and harboring CHD7 mutations, to elucidate potential pathogenic mechanisms.MethodsA case-control study was conducted with three groups: seven children with CHD7-mutant CHD-NDA, 24 children with isolated CHD, and nine healthy controls. Serum metabolomic profiling was performed using untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) in both positive and negative ion modes.ResultsThe metabolomic profiles showed a tendency toward separation among the CHD7-mutant CHD-NDA, isolated CHD, and healthy control groups. Candidate differential metabolites were mainly enriched in steroid hormone biosynthesis, glyoxylate and dicarboxylate metabolism, ascorbate and aldarate metabolism, and glutathione metabolism in the CHD7-mutant group compared with the isolated CHD group. Compared with healthy controls, the CHD7-mutant group also showed candidate alterations related to steroid hormone biosynthesis, riboflavin metabolism, and folate biosynthesis. Two overlapping candidate metabolites, 11-deoxycortisol and 2-hydroxyestrone, were identified across pairwise comparisons and may represent potential metabolic markers related to steroid metabolism.ConclusionThe metabolic disturbances observed in children with CHD7-associated CHD-NDA may be related to steroid metabolism and hypothalamic-pituitary axis regulation. These preliminary findings suggest a potential metabolic link between CHD7 mutations, cardiac phenotypes, and neurodevelopmental abnormalities, warranting further validation in larger, sex-matched cohorts.