IEMbase 0360: ST3GAL5-related GM3 synthase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 360 |
| Nosology | 18.3.00.01 |
| Gene | ST3GAL5 |
| External IDs | OMIM:609056; ORPHA:370938 |
| Generated mapping | MAPPED/HIGH to GM3_Synthase_Deficiency.yaml |
| Candidate DisMech targets | GM3_Synthase_Deficiency.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents ST3GAL5-CDG, also listed as Amish infantile epilepsy, an autosomal recessive lactosylceramide alpha-2,3-sialyltransferase deficiency. Characteristic rows include cortical atrophy on MRI, failure to thrive, GM3 activity, GM3 ganglioside, intractable epilepsy, and lactosylceramide.
Additional clinical rows include acquired microcephaly, choreoathetosis, sensorineural deafness, intellectual disability, optic nerve hypoplasia, pigmentation, psychomotor regression, and visual impairment. Biochemical rows include GM3 activity, GM3 ganglioside, lactate, and lactosylceramide. No treatment rows are present.
DisMech phenotype coverage
The generated MAPPED/HIGH status is correct. DisMech has a GM3 synthase deficiency file for biallelic ST3GAL5 disease, describing loss of GM3 synthase conversion of lactosylceramide to GM3, depletion of GM3 and downstream gangliosides, and severe infantile neurodevelopmental disease.
Local coverage includes refractory seizures, developmental delay/regression, profound intellectual disability, feeding difficulty, failure to thrive, visual and hearing impairment, movement disorder, hypotonia, abnormal skin pigmentation, reduced GM3 synthase activity, reduced GM3 ganglioside, and lactosylceramide/downstream ganglioside abnormalities.
Concordance and completeness
Judgement: correct mapping with high concordance.
The resources agree on ST3GAL5 identity, autosomal recessive inheritance, GM3 synthase deficiency, lactosylceramide/GM3 ganglioside biology, infantile refractory epilepsy, neurodevelopmental regression or delay, failure to thrive, hearing and visual involvement, movement disorder, microcephaly/cortical atrophy context, and abnormal pigmentation.
One identifier detail needs review: IEMbase reports ORPHA:370938, while the local DisMech file uses ORPHA:370933. The OMIM, gene, disease name, and mechanism all support the mapping, but the ORPHA discrepancy should be checked before reusing the ORPHA code.
Curation actions
- Keep the mapping to
GM3_Synthase_Deficiency.yaml. - Review the ORPHA identifier discrepancy,
ORPHA:370938in IEMbase versus localORPHA:370933, before any identifier update. - Consider future enrichment with lactate, plasma GM3/lactosylceramide row placement, optic nerve hypoplasia, acquired microcephaly, choreoathetosis, and cortical atrophy after source verification.