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IEMbase 0688: NDUFS2-related NADH dehydrogenase iron-sulfur protein 2 deficiency

Scope

Field Value
IEMbase ID 688
Nosology 7.1.04.02
Nosology code IEM0416
Gene NDUFS2
External IDs OMIM:618228; ORPHA:70474
Generated mapping CANDIDATE to COX4I1-Related_COX_Deficiency.yaml
Candidate DisMech targets Broad complex I/Leigh context only; no exact NDUFS2 target
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents autosomal recessive NDUFS2-related NADH dehydrogenase iron-sulfur protein 2 deficiency, also labeled mitochondrial complex I deficiency, nuclear type 6.

Biochemical rows include decreased fibroblast complex I activity and increased plasma lactate across all ages. Clinical rows include encephalopathy, hypotonia, Leigh syndrome, liver dysfunction, parkinsonism, and characteristic hypertrophic cardiomyopathy and myopathy.

DisMech phenotype coverage

No exact NDUFS2 or MC1DN6 local target was identified.

Leigh_Syndrome.yaml overlaps at the syndrome level but does not capture this gene-specific complex I subunit disease. The generated COX4I1-Related_COX_Deficiency.yaml candidate is a complex IV regulatory-subunit disorder, not NDUFS2-related complex I disease.

Concordance and completeness

Judgement: true local gap.

The IEMbase row should be kept distinct from complex IV deficiency and from generic Leigh syndrome, especially because it includes liver dysfunction, parkinsonism, myopathy, and hypertrophic cardiomyopathy.

Curation actions

  • Add a dedicated NDUFS2/MC1DN6 target if curated.
  • Reject COX4I1-related complex IV deficiency as exact coverage.
  • Preserve decreased complex I activity, increased lactate, encephalopathy, hypotonia, Leigh syndrome, liver dysfunction, parkinsonism, hypertrophic cardiomyopathy, and myopathy.