Untargeted Metabolomic and Lipidomic Profiling Reveals Distinct Biochemical Patterns in Treated Biotinidase...

Area of Science:

• Biochemistry
• Genetics
• Metabolomics
• Lipidomics

Background:

• Biotinidase deficiency (BD) is an inherited disorder affecting biotin metabolism.
• While biotin treatment prevents severe symptoms, its long-term biochemical impact is not well understood.

Purpose of the Study:

• To investigate the long-term biochemical effects of biotin supplementation in children with biotinidase deficiency.
• To identify distinct metabolic and lipidomic signatures in treated patients.

Main Methods:

• Untargeted metabolomic and lipidomic profiling of 54 pediatric patients with genetically confirmed BD on biotin therapy.
• Comparison with 30 age- and sex-matched healthy controls.
• Multivariate analyses and pathway enrichment to identify biochemical differences.

Main Results:

• Distinct metabolic signatures were observed, involving amino acid, energy, and lipid metabolism.
• Reduced levels of certain amino acids and TCA cycle intermediates were noted.
• Elevated levels of octopine, sphingolipids, phosphatidylcholines, long-chain fatty acids, and acylcarnitines were found, indicating lipid remodeling.
• Octopine was a key metabolite differentiating the groups.

Conclusions:

• Clinically stable children with biotinidase deficiency on biotin therapy exhibit unique metabolic and lipidomic patterns.
• These patterns suggest metabolic adaptations to sustained biotin exposure rather than ongoing disease pathology.
• Octopine and specific lipids may serve as biomarkers for this adaptive state, informing personalized monitoring.