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IEMbase 0687: NDUFS1-related NADH dehydrogenase iron-sulfur protein 1 deficiency

Scope

Field Value
IEMbase ID 687
Nosology 7.1.03.02
Nosology code IEM0415
Gene NDUFS1
External IDs OMIM:618226 for NDUFS1/MC1DN5; IEMbase source lists OMIM:618229; ORPHA:255241
Generated mapping CANDIDATE to COX8A-Related_COX_Deficiency.yaml
Candidate DisMech targets Broad complex I/Leigh context only; no exact NDUFS1 target
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents autosomal recessive NDUFS1-related NADH dehydrogenase iron-sulfur protein 1 deficiency, also labeled mitochondrial complex I deficiency, nuclear type 5.

The cached IEMbase record lists OMIM:618229, which appears to correspond to NDUFV2/MC1DN7 rather than NDUFS1/MC1DN5. The scope table records the expected NDUFS1/MC1DN5 identifier while preserving the source anomaly.

Biochemical rows show decreased fibroblast complex I activity and increased plasma lactate across all ages. Clinical rows include hypertrophic cardiomyopathy, encephalopathy, hypotonia, liver dysfunction, myopathy, and characteristic leukodystrophy and optic neuropathy.

DisMech phenotype coverage

No exact NDUFS1 or MC1DN5 local target was identified.

Leigh_Syndrome.yaml provides broad complex I/Leigh context, and local complex IV files model other respiratory-chain defects. There is no NDUFS1-specific entry or subtype.

The generated COX8A-Related_COX_Deficiency.yaml candidate is a wrong-complex match. COX8A is complex IV, while NDUFS1 is a complex I iron-sulfur subunit.

Concordance and completeness

Judgement: true local gap.

The phenotype package combines complex I biochemical deficiency, lactate, cardiac/myopathic disease, liver dysfunction, encephalopathy/hypotonia, leukodystrophy, and optic neuropathy. Generic Leigh coverage is insufficient for NDUFS1 completeness.

Curation actions

  • Add a dedicated NDUFS1/MC1DN5 target if curated.
  • Reject COX8A-related complex IV deficiency as exact coverage.
  • Preserve decreased complex I activity, increased lactate, hypertrophic cardiomyopathy, myopathy, liver dysfunction, encephalopathy, hypotonia, leukodystrophy, and optic neuropathy.