VPS51-Related Pontocerebellar Hypoplasia-CDG Deep Research Fallback

Scope

No provider-generated deep research artifact was present on the WP-068 branch. This fallback audit documents the literature scope used to curate and review the VPS51-related entry from cached PubMed references.

Evidence Scope Used For Curation

• PMID:30624672 for the original biallelic VPS51 case, reduced assembled GARP/EARP complexes, mannose-6-phosphate receptor redistribution, lysosomal swelling, and the clinical phenotype including developmental delay, microcephaly, hypotonia, epilepsy, cortical visual impairment, pontocerebellar abnormalities, failure to thrive, liver dysfunction, lower extremity edema, and dysmorphic features.
• PMID:40565173 for later affected siblings with a homozygous VPS51 variant, fibroblast proteomics showing vesicular, lysosomal, and mitochondrial pathway disruption, and additional phenotypes including thin corpus callosum, severe intellectual disability, epilepsy, microcephaly, hearing loss, and dysphagia.
• PMID:34161137 for the mechanistic link between GARP disruption and abnormal cellular and serum glycoprotein glycosylation.

Curation Conclusions

The supported model is biallelic VPS51 dysfunction causing combined GARP/EARP tethering-complex deficiency. Patient-cell evidence supports impaired endosome-derived cargo sorting, lysosomal abnormalities, and downstream Golgi glycoprotein processing defects. The curated phenotype set should include the core neurologic and growth features plus sensory, hepatic, edema, dysmorphic, hearing, and swallowing features reported in the cached literature.