Metabolic landscape of inborn errors of metabolism

Genotype-specific metabolomic alterations were uncovered across 57 different inborn errors of metabolism in a Mendelian disease clinic cohort of 474 subjects, using plasma and fibroblast metabolomics.

• Why it matters: Inborn errors of metabolism are caused by inherited defects, but linking genomic variants to specific metabolic consequences remains challenging for diagnosis and mechanistic understanding.
• What they did: The study profiled plasma and patient-derived fibroblast lines from 242 known or suspected IEM patients plus family members, then analyzed metabolite–metabolite associations and inter-metabolite congruence.
• The result: Departures from inter-metabolite congruence and shared metabolomic anomaly patterns helped pinpoint metabolic defects and categorize patients with suspected IEMs, with systemic versus cell-autonomous differences between plasma and fibroblasts.

AI summary of the abstract · may contain errors · not medical advice · read the paper.