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IEMbase 0683: FOXRED1-related mitochondrial complex I deficiency, nuclear type 19

Scope

Field Value
IEMbase ID 683
Nosology 7.1.07.01
Nosology code IEM0443
Gene FOXRED1
External IDs OMIM:618241; ORPHA:255241
Generated mapping CANDIDATE to PET117-Related_COX_Deficiency.yaml
Candidate DisMech targets Broad complex I/Leigh context only; no exact FOXRED1 target
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents autosomal recessive FOXRED1-related mitochondrial complex I deficiency, nuclear type 19.

Biochemical rows include decreased fibroblast complex I activity and increased plasma lactate across all ages. Clinical rows include epilepsy, hypotonia, Leigh syndrome, characteristic hypertrophic cardiomyopathy in infancy/childhood, characteristic cerebellar atrophy on MRI across all ages, and characteristic pulmonary hypertension from infancy through adolescence.

DisMech phenotype coverage

No exact FOXRED1 or MC1DN19 target was identified.

Leigh_Syndrome.yaml provides broad overlap for complex I deficiency, mitochondrial energy failure, lactic acidosis, hypotonia, seizures, basal ganglia/brainstem vulnerability, and cardiomyopathy-associated Leigh syndrome. It does not model FOXRED1 or the pulmonary-hypertension/cerebellar-atrophy phenotype package.

The generated PET117-Related_COX_Deficiency.yaml candidate is a complex IV assembly-factor disorder and should be rejected as exact coverage.

Concordance and completeness

Judgement: true local gap with broad Leigh/complex I context only.

The IEMbase row is a gene-specific complex I deficiency with useful extra features beyond generic Leigh syndrome: hypertrophic cardiomyopathy, cerebellar atrophy, and pulmonary hypertension.

Curation actions

  • Add a dedicated FOXRED1/MC1DN19 target if curated.
  • Reject PET117-related complex IV deficiency as exact coverage.
  • Preserve decreased complex I activity, increased lactate, epilepsy, hypotonia, Leigh syndrome, hypertrophic cardiomyopathy, cerebellar atrophy, and pulmonary hypertension.
  • Use broad Leigh syndrome context only for shared mitochondrial neurologic features.