IEMbase 0172: ETHE1-related ethylmalonic encephalopathy
Scope
| Field | Value |
|---|---|
| IEMbase ID | 172 |
| Nosology | 1.5.1.01 |
| Gene | ETHE1 |
| External IDs | OMIM:602473; ORPHA:51188 |
| Generated mapping | UNMAPPED; best candidate Chronic_Traumatic_Encephalopathy.yaml |
| Candidate DisMech targets | None valid |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as ETHE1-related mitochondrial sulfur dioxygenase deficiency, with alternate labels ethylmalonic encephalopathy and ETHE1. Treatability is marked yes.
The biochemical profile is distinctive and extensive: urinary ethylmalonic acid is strongly increased; urinary 2-methylbutyrylglycine, isovalerylglycine, methylsuccinic acid, S-sulfocysteine, taurine, C4 butyrylcarnitine, C4 isobutyrylcarnitine, C5 2-methylbutyrylcarnitine, C5 isovalerylcarnitine, C5-DC glutarylcarnitine, lactate, thiosulfate, hydrogen sulfide, and sulfite are increased in relevant age bands. Clinical rows include axial hypotonia, dystonia, failure to thrive, hematuria, patchy T2 white matter, brainstem, and cerebellar changes, neonatal seizures, psychomotor delay, seizures, spastic tetraplegia, symmetric basal ganglia lesions, hemorrhagic chronic diarrhea, orthostatic acrocyanosis, and petechiae. Treatment rows list antibiotics, liver transplantation, and N-acetylcysteine.
DisMech phenotype coverage
No valid local DisMech target was found. The generated best candidate,
Chronic_Traumatic_Encephalopathy.yaml, is a lexical false positive. It
models repetitive head trauma with tau/TDP-43 pathology and progressive
neurodegeneration; it has no ETHE1, sulfide detoxification, ethylmalonic acid,
or vascular-gastrointestinal phenotype overlap that would justify mapping.
Concordance and completeness
Judgement: true local gap.
IEMbase provides a high-value, treatable ETHE1 disease record with a strong metabolic, neurologic, vascular, and gastrointestinal signature. DisMech lacks the disease, and no current local umbrella appears to cover it.
Curation actions
- Do not map this record to chronic traumatic encephalopathy.
- Prioritize a future ETHE1/ethylmalonic encephalopathy entry.
- Expected future coverage: ETHE1 loss of mitochondrial sulfur dioxygenase activity, hydrogen sulfide/thiosulfate/sulfite accumulation, ethylmalonic aciduria, C4/C5 acylcarnitine abnormalities, lactic acidosis, basal ganglia and white matter disease, acrocyanosis, petechiae, hemorrhagic chronic diarrhea, neurologic delay/seizures/spasticity, and treatment context for antibiotics, N-acetylcysteine, and liver transplantation.