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

OBJECTIVE: This 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. METHODS: A 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. RESULTS: The 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. CONCLUSION: The 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.