IEMbase 0690: NDUFS4-related NADH dehydrogenase iron-sulfur protein 4 deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 690 |
| Nosology | 7.1.08.01 |
| Nosology code | IEM0420 |
| Gene | NDUFS4 |
| External IDs | OMIM:252010; ORPHA:255241 |
| Generated mapping | UNMAPPED |
| Candidate DisMech targets | Partial gene-level coverage in Leigh_Syndrome.yaml; no standalone NDUFS4 target |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents autosomal recessive NDUFS4-related NADH dehydrogenase iron-sulfur protein 4 deficiency, also labeled mitochondrial complex I deficiency, nuclear type 1.
Biochemical rows include decreased fibroblast complex I activity, decreased fibroblast complex III activity, increased plasma lactate, and low-to-normal plasma glucose in early ages. Clinical rows include basal ganglia MRI abnormalities, failure to thrive, hypotonia, and characteristic hypertrophic cardiomyopathy, lactic acidosis, and Leigh syndrome.
DisMech phenotype coverage
Leigh_Syndrome.yaml contains partial gene-level NDUFS4 coverage. Its genetic
section states that biallelic NDUFS4 loss-of-function causes complex
I-deficient Leigh syndrome, with evidence from the Ndufs4 mouse model. The
entry also covers shared Leigh features including complex I deficiency,
lactic acidosis, basal ganglia lesions, hypotonia, failure to thrive, and
cardiomyopathy.
There is no standalone NDUFS4 disease target or MC1DN1 subtype with the full IEMbase biochemical and phenotype set.
Concordance and completeness
Judgement: partial broad Leigh coverage only.
The NDUFS4 gene-to-Leigh relationship is represented locally, but row-level completeness is not established. IEMbase adds complex III activity decrease, low-to-normal glucose, age-banded fibroblast complex I activity, and hypertrophic cardiomyopathy emphasis.
Curation actions
- Keep
Leigh_Syndrome.yamlas partial gene/syndrome context. - Add a dedicated NDUFS4/MC1DN1 target or subtype if full disease-level coverage is desired.
- Preserve decreased complex I and complex III activity, increased lactate, low-to-normal glucose, basal ganglia abnormalities, failure to thrive, hypotonia, hypertrophic cardiomyopathy, lactic acidosis, and Leigh syndrome.