C12ORF54 mediates lipid droplet delivery to lysosomes with mutation causing childhood-onset metabolic dysfunction-associated steatotic liver disease.
Ashish Negi, Abhishek Kumar, Yogendra Pratap Mathuria et al.
✦ AI-curated · Sources linked
Case in brief
A 2-year-old boy presented with metabolic dysfunction-associated steatotic liver disease (MASLD) and was found to have a homozygous missense variant in the C12ORF54 gene. This mutation disrupted the protein's ability to bind lipid droplets and lysosomes, leading to lipid accumulation, oxidative stress, and cell death. The condition was linked to defective lysosomal lipid droplet deposition, highlighting a novel mechanism in childhood liver disease.
What made this case unusual
The case highlights a previously unrecognized genetic mechanism involving the C12ORF54 gene, which is crucial for lipid droplet turnover and lysosomal targeting, linking it to childhood-onset MASLD.
Diagnostic / clinical pearl
Clinicians should consider genetic testing for rare mutations in cases of childhood-onset metabolic liver diseases, as they may reveal novel pathogenic mechanisms.
Why it matters
Understanding the role of C12ORF54 in lipid metabolism could inform future research on metabolic liver diseases and potential therapeutic targets.