Integration of multi-omics layers empowers precision diagnosis through unveiling pathogenic mechanisms on maple syrup urine disease.

ABSTRACT: Maple syrup urine disease (MSUD) is a rare inherited metabolic disorder characterized by deficient activity of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex, required to metabolize the amino acids leucine, isoleucine, and valine. Despite its profound metabolic implications, the molecular alterations underlying this metabolic impairment had not yet been completely elucidated. We performed a comprehensive multi-omics integration analysis, including genomic, epigenomic, and transcriptomic data from fibroblasts derived from a cohort of MSUD patients and unaffected controls to genetically characterize an MSUD case and to unravel the MSUD pathophysiology. MSUD patients exhibit a defined episignature that reshapes the global DNA methylation landscape, resulting in the stimulatio

SUBMITTER: Tejedor JR 

PROVIDER: S-EPMC11670297 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature