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IEMbase 0697: NDUFA9-related NADH dehydrogenase alpha subcomplex subunit 9 deficiency

Scope

Field Value
IEMbase ID 697
Nosology 7.1.12.01
Nosology code IEM0424
Gene NDUFA9
External IDs OMIM:618247 for NDUFA9/MC1DN26; IEMbase source lists OMIM:256000; ORPHA:255241
Generated mapping CANDIDATE to COX11-Related_COX_Deficiency.yaml
Candidate DisMech targets Broad complex I/Leigh context only; no exact NDUFA9 target
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents autosomal recessive NDUFA9-related NADH dehydrogenase alpha subcomplex subunit 9 deficiency, also labeled mitochondrial complex I deficiency, nuclear type 26.

The source lists OMIM:256000, while MONDO resolves mitochondrial complex I deficiency nuclear type 26 to OMIM:618247 and NDUFA9. The broad source identifier should therefore be checked before downstream use.

Biochemical rows show decreased fibroblast complex I activity and increased plasma lactate through childhood. Clinical rows include abnormal brain MRI, brainstem lesions, dysarthria, dysphagia, lactic acidosis, Leigh syndrome, dystonia, and retinitis pigmentosa.

DisMech phenotype coverage

No exact NDUFA9 or MC1DN26 local target was identified.

Leigh_Syndrome.yaml supplies broad overlap for complex I-linked Leigh disease, lactate elevation, brainstem lesions, movement disorder, dysphagia, and retinal/neurologic involvement, but it does not model NDUFA9 as a causal gene.

The generated COX11-Related_COX_Deficiency.yaml candidate is a complex IV copper-delivery disorder, not an NDUFA9 complex I subunit disorder.

Concordance and completeness

Judgement: true local gap with broad Leigh overlap only.

The IEMbase phenotype signal combines a complex I enzyme defect with Leigh syndrome, brainstem MRI disease, bulbar dysfunction, dystonia, and retinitis pigmentosa. That combination should not be collapsed into generic Leigh or into COX11-related complex IV deficiency.

Curation actions

  • Add a dedicated NDUFA9/MC1DN26 target if curated.
  • Reject COX11-related complex IV deficiency as exact coverage.
  • Preserve the source OMIM discrepancy for review before downstream identifier use.
  • Preserve decreased fibroblast complex I activity, increased plasma lactate, brain MRI abnormalities, brainstem lesions, dysarthria, dysphagia, lactic acidosis, Leigh syndrome, dystonia, and retinitis pigmentosa.