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IEMbase 0678: NDUFAF2-related complex I assembly factor 2 deficiency

Scope

Field Value
IEMbase ID 678
Nosology 7.1.02.01
Nosology code IEM0438
Gene NDUFAF2
External IDs OMIM:618233; ORPHA:255241
Generated mapping CANDIDATE to COX14-Related_COX_Deficiency.yaml
Candidate DisMech targets Broad complex I/Leigh context only; no exact NDUFAF2 target
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents autosomal recessive NDUFAF2-related complex I assembly factor 2 deficiency, also labeled mitochondrial complex I deficiency, nuclear type 10.

Biochemical rows show decreased fibroblast complex I activity and increased plasma lactate from neonatal through adolescent ages. Clinical rows include hypotonia, renal tubular acidosis, possible respiratory insufficiency from muscle weakness or diaphragm paralysis, and characteristic ataxia, basal ganglia MRI abnormalities, encephalopathy, nystagmus, and optic atrophy.

DisMech phenotype coverage

No exact NDUFAF2 or MC1DN10 target was identified.

Leigh_Syndrome.yaml covers broad complex I-linked Leigh biology and several overlapping neurologic features, including basal-ganglia involvement, hypotonia, movement disorder, ataxia, lactic acidosis, and seizures. That is syndrome context, not a gene-specific NDUFAF2 disease model.

The generated COX14-Related_COX_Deficiency.yaml candidate is a wrong-complex match. COX14 is a complex IV assembly factor and does not cover NDUFAF2-related complex I assembly failure.

Concordance and completeness

Judgement: true local gap.

The strongest preservation points are the complex I enzyme readout and the NDUFAF2-specific phenotype prompts that are not guaranteed by generic Leigh coverage: renal tubular acidosis, respiratory insufficiency/diaphragm weakness, nystagmus, and optic atrophy.

Curation actions

  • Add a dedicated NDUFAF2/MC1DN10 target if curated.
  • Reject COX14-related complex IV deficiency as exact coverage.
  • Preserve decreased fibroblast complex I activity, lactate, renal tubular acidosis, respiratory insufficiency, basal-ganglia lesions, nystagmus, optic atrophy, ataxia, and encephalopathy.
  • Use broad Leigh context only for shared mitochondrial neurologic features.