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IEMbase 0677: NDUFAF1-related complex I assembly factor 1 deficiency

Scope

Field Value
IEMbase ID 677
Nosology 7.1.01.01
Nosology code IEM0437
Gene NDUFAF1
External IDs OMIM:618234; ORPHA:289527
Generated mapping CANDIDATE to COX20-Related_COX_Deficiency.yaml
Candidate DisMech targets Broad complex I/Leigh context only; no exact NDUFAF1 target
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents autosomal recessive NDUFAF1-related complex I assembly factor 1 deficiency, also labeled mitochondrial complex I deficiency, nuclear type 11.

The biochemical rows show decreased fibroblast complex I activity and increased plasma lactate from the neonatal period through adolescence. Clinical rows include hypotonia, lactic acidosis, MELAS-like features, and characteristic cardiomyopathy across the same age range, plus characteristic neonatal/infantile failure to thrive.

DisMech phenotype coverage

No exact NDUFAF1 or MC1DN11 target was identified.

Leigh_Syndrome.yaml provides broad complex I and mitochondrial energy-failure context, including complex I deficiency, lactic acidosis, hypotonia, basal ganglia vulnerability, and cardiomyopathy as a Leigh subtype. ACAD9_Deficiency.yaml also discusses complex I assembly biology and mentions NDUFAF1 as an ACAD9 binding partner in the MCIA complex. Neither file is disease-level coverage for NDUFAF1 deficiency.

The generated COX20-Related_COX_Deficiency.yaml candidate is a complex IV/COX false positive and should not be used.

Concordance and completeness

Judgement: true local gap with broad complex I context available.

The IEMbase row is specifically an assembly-factor complex I defect. Existing complex IV files are wrong-complex matches, while Leigh and ACAD9 entries can only support generic mechanism context.

Curation actions

  • Add a dedicated NDUFAF1/MC1DN11 target if curated.
  • Reject COX20-related complex IV deficiency as exact coverage.
  • Preserve decreased fibroblast complex I activity, increased plasma lactate, cardiomyopathy, failure to thrive, hypotonia, lactic acidosis, and MELAS-like features.
  • Use Leigh_Syndrome.yaml only as broad syndrome context.