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IEMbase 0665: ECHS1-related mitochondrial short-chain enoyl-CoA hydratase 1 deficiency

Scope

Field Value
IEMbase ID 665
Nosology 1.3.01.01
Nosology code IEM0119
Gene ECHS1
External IDs OMIM:616277; ORPHA:255241
Generated mapping UNMAPPED; best candidate Beta-Ketothiolase_Deficiency.yaml
Candidate DisMech targets ECHS1_Deficiency.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents autosomal recessive ECHS1-related mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, also labeled crotonase deficiency.

The biochemical signal includes increased plasma lactate and pyruvate, normal lactate/pyruvate ratio, increased urinary 2,3-dihydroxy-2-methylbutyric acid, and increased urinary S-(2-carboxypropyl)-cysteine. Clinical rows include neonatal hypotonia, dystonia, seizures, apnea, brain MRI abnormalities, basal-ganglia lesions, psychomotor regression, hypertrophic cardiomyopathy, possible hearing loss, and possible optic atrophy.

DisMech phenotype coverage

ECHS1_Deficiency.yaml is an exact local target. It models biallelic ECHS1 loss, mitochondrial short-chain enoyl-CoA hydratase/crotonase dysfunction, Leigh or Leigh-like basal ganglia disease, developmental delay or regression, dystonia, hypotonia, seizures, lactic acidosis, and toxic intermediates from valine catabolism including methacrylyl-CoA and acryloyl-CoA.

The generated Beta-Ketothiolase_Deficiency.yaml candidate is a pathway-neighbor false positive. It is adjacent in organic-acid and ketone/isoleucine metabolism, but it is not the ECHS1 disease entity.

Concordance and completeness

Judgement: false negative from stale generated mapping; current DisMech has an exact high-concordance ECHS1 target.

IEMbase adds useful granularity for neonatal age-band timing, the normal lactate/pyruvate-ratio row, cardiomyopathy, hearing loss, optic atrophy, apnea, and specific urine metabolites. These should be reviewed as enrichment prompts for ECHS1_Deficiency.yaml.

Curation actions

  • Resolve this IEMbase record to ECHS1_Deficiency.yaml.
  • Do not use beta-ketothiolase deficiency as the target.
  • Preserve the S-(2-carboxypropyl)-cysteine and 2,3-dihydroxy-2-methylbutyric-acid biomarkers.
  • Check whether cardiomyopathy, apnea, hearing loss, optic atrophy, and normal lactate/pyruvate ratio should be added or made more explicit locally.