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GM3 synthase deficiency

GM3 Synthase Deficiency Deep Research Fallback

⚠️ Fallback MONDO:0018274

GM3 Synthase Deficiency Deep Research Fallback

Date: 2026-05-04T13:48Z

Provider Attempts

  • timeout 180 uv run deep-research-client research --template templates/disease_pathophysiology_research.md --var disease_name=GM3 synthase deficiency --var mondo_id=MONDO:0018274 --var category=Mendelian --provider falcon --output research/GM3_Synthase_Deficiency-deep-research-falcon.md --separate-citations research/GM3_Synthase_Deficiency-deep-research-falcon.md.citations.md
  • Result: timed out after the bounded 180-second run.
  • Completed artifact: none.
  • timeout 180 uv run deep-research-client research --template templates/disease_pathophysiology_research.md --var disease_name=GM3 synthase deficiency --var mondo_id=MONDO:0018274 --var category=Mendelian --provider openai --output research/GM3_Synthase_Deficiency-deep-research-openai.md --separate-citations research/GM3_Synthase_Deficiency-deep-research-openai.md.citations.md
  • Result: timed out after the bounded 180-second run.
  • Completed artifact: none.

No provider-generated deep-research narrative completed within the bounded runtime. Curation therefore proceeded from regenerated structured Orphanet evidence and sequentially fetched PubMed caches, without hand-editing any references_cache/*.md files.

Evidence Scope Used For Curation

Structured Source

  • ORPHA:370933 GM3 synthase deficiency structured record
  • Exact MONDO cross-reference: MONDO:0018274
  • Exact OMIM cross-reference: OMIM:609056
  • Synonym: ST3GAL5-CDG
  • Inheritance: autosomal recessive
  • Gene assertion: ST3GAL5, disease-causing germline loss of function
  • Definition supports impaired complex ganglioside synthesis with early irritability, poor feeding, failure to thrive, refractory epilepsy, later growth impairment, developmental delay or regression, profound intellectual disability, deafness, abnormal skin pigmentation, visual impairment, choreoathetosis, and hypotonic tetraparesis.

PubMed Records

  • PMID:15502825
  • Original Amish infantile-onset symptomatic epilepsy syndrome report.
  • Supports autosomal recessive disease, truncating SIAT9/ST3GAL5 variant, GM3 synthase's role in complex ganglioside biosynthesis, absent GM3 synthase activity, absent GM3 ganglioside and derivatives, and increased upstream glycosphingolipid species.
  • PMID:18480157
  • Patient fibroblast study.
  • Supports severe ganglioside depletion, lack of compensatory alternative ganglioside synthesis, reduced EGF-induced proliferation and migration, reduced EGFR binding, and dampened EGFR activation.
  • PMID:24026681
  • Salt and pepper syndrome ST3GAL5 paper.
  • Supports severe intellectual disability, epilepsy, choreoathetosis, dysmorphic and pigmentation features, ST3GAL5 p.E332K, complete GM3 lack in patient fibroblasts, collateral glycolipid and glycoprotein glycosylation changes, and increased apoptosis in zebrafish brain regions after st3gal5 knockdown.
  • PMID:30209782
  • Human oral ganglioside supplementation study.
  • Supports absence of GM3 and downstream derivatives, severe irritability, intractable seizures, profound intellectual disability, oral ganglioside enriched dairy supplementation, improved growth and development, transient benefit, and need for endogenous ganglioside restoration strategies.
  • PMID:30576498
  • Variant enzyme-assay paper.
  • Supports ST3GAL5-CDG as a GM3 synthase disorder, failure to thrive and severe hearing, visual, motor, and cognitive impairment in a reported patient, and complete loss of enzyme activity across pathogenic variants.
  • PMID:34906476
  • Non-Amish patient cohort.
  • Supports biallelic ST3GAL5 loss of function, 16 affected non-Amish patients, severe to profound intellectual disability in all patients, hyperkinetic movement disorder in 14 of 16, epilepsy in 11 of 16, microcephaly in 9 of 16, progressive skin pigmentation anomalies, optic atrophy or pale papillae, and hearing loss.
  • PMID:35628171
  • Review of human disease and mouse models.
  • Supports ST3GAL5/GM3 synthase conversion of lactosylceramide to GM3, neural ganglioside biology, human progressive microcephaly, intellectual disability, dyskinetic movements, blindness, deafness, intractable seizures, pigment changes, and mouse-model limitations.
  • PMID:36833282
  • Saudi family report.
  • Supports ST3GAL5-associated salt and pepper developmental regression syndrome with epilepsy, profound intellectual disability, choreoathetosis, scoliosis, pigmentation, dysmorphism, novel homozygous ST3GAL5 variant, speech delay, and developmental delay.
  • PMID:37676252
  • Patient-derived iPSC/neural crest cell study.
  • Supports undetectable GM3 and GM3-derived gangliosides, elevated LacCer precursor, altered cell-surface proteome, O-GlcNAcylation, receptor tyrosine kinase abundance, increased apoptosis, and EGFR-inhibitor sensitivity in GM3SD neural lineage cells.
  • PMID:39119456
  • Dietary ganglioside supplementation mouse study.
  • Supports absence of GM3 and downstream derivatives, clinical features in affected individuals, prior human supplementation improvements, improved cognitive function in supplemented GM3 synthase-deficient mice, and increased ganglioside levels plus hippocampal neurogenesis.

Integration Notes

The YAML models GM3 synthase deficiency as a ST3GAL5 loss-of-function glycosphingolipid biosynthesis disorder. ST3GAL5 encodes lactosylceramide alpha-2,3-sialyltransferase activity, which produces ganglioside GM3 from lactosylceramide. Loss of that enzyme depletes GM3 and downstream ganglioside derivatives, alters broader glycosphingolipid and glycoprotein glycosylation, and perturbs membrane and receptor signaling in patient-derived neural lineage cells. The curated phenotype model emphasizes the severe infantile neurologic, growth, sensory, movement, and pigmentation phenotype supported by Orphanet and clinical cohorts.

Treatment evidence remains limited. The only disease-directed human treatment evidence found in the bounded literature scope was oral ganglioside-enriched dairy supplementation, which reported early growth and developmental improvements that appeared transient. The YAML therefore avoids a broad supportive-care treatment claim unless a direct management reference is added, and records autosomal recessive genetic counseling separately.