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IEMbase 0680: NDUFAF4-related complex I assembly factor 4 deficiency

Scope

Field Value
IEMbase ID 680
Nosology 7.1.04.01
Nosology code IEM0440
Gene NDUFAF4
External IDs OMIM:618237; ORPHA:2609
Generated mapping CANDIDATE to COX8A-Related_COX_Deficiency.yaml
Candidate DisMech targets Broad complex I/Leigh context only; no exact NDUFAF4 target
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents autosomal recessive NDUFAF4-related complex I assembly factor 4 deficiency, also labeled mitochondrial complex I deficiency, nuclear type 15.

The biochemical rows show decreased fibroblast complex I activity and increased plasma lactate in neonatal and infantile periods. Clinical rows include Leigh syndrome, characteristic cardiomyopathy, and characteristic encephalomyopathy.

DisMech phenotype coverage

No exact NDUFAF4 or MC1DN15 local target was identified.

Leigh_Syndrome.yaml provides broad syndrome context for complex I deficiency, lactic acidosis, basal ganglia vulnerability, and cardiomyopathy-associated Leigh presentations. It does not identify NDUFAF4 or the MC1DN15 disease entity.

The generated COX8A-Related_COX_Deficiency.yaml candidate is a wrong-complex match. COX8A is a complex IV structural-subunit deficiency and should not be used for NDUFAF4-related complex I assembly failure.

Concordance and completeness

Judgement: true local gap with broad Leigh context only.

The core IEMbase package is neonatal/infantile complex I enzyme deficiency with lactate elevation, Leigh syndrome, encephalomyopathy, and cardiomyopathy.

Curation actions

  • Add a dedicated NDUFAF4/MC1DN15 target if curated.
  • Reject COX8A-related complex IV deficiency as exact coverage.
  • Preserve decreased fibroblast complex I activity, increased lactate, Leigh syndrome, encephalomyopathy, and cardiomyopathy.
  • Avoid treating generic Leigh syndrome as gene-specific completeness.