IEMbase 0682: NDUFAF6-related complex I assembly factor 6 deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 682 |
| Nosology | 7.1.06.01 |
| Nosology code | IEM0442 |
| Gene | NDUFAF6 |
| External IDs | OMIM:618239; ORPHA:255241 |
| Generated mapping | UNMAPPED; best candidate Fanconi_Renotubular_Syndrome.yaml |
| Candidate DisMech targets | Partial gene-level coverage in Fanconi_Renotubular_Syndrome.yaml#FRTS5; exact MC1DN17/Leigh phenotype gap |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents autosomal recessive NDUFAF6-related complex I assembly factor 6 deficiency, also labeled mitochondrial complex I deficiency, nuclear type 17.
Biochemical rows include decreased fibroblast complex I activity and increased plasma lactate from neonatal through adolescent ages. Clinical rows include basal ganglia MRI abnormalities, bilateral striatal necrosis, epilepsy, Leigh syndrome, psychomotor retardation, and characteristic ataxia, dystonia, and lactic acidosis.
DisMech phenotype coverage
Fanconi_Renotubular_Syndrome.yaml contains real NDUFAF6 coverage under FRTS5,
the Acadian variant of Fanconi syndrome. That local subtype describes a
homozygous non-coding NDUFAF6 splicing variant causing loss of the
mitochondria-localized isoform, respiratory-chain complex I deficiency,
generalized proximal tubular dysfunction from birth, progressive chronic kidney
disease, and pulmonary interstitial fibrosis.
This is not complete coverage for the IEMbase row. IEMbase is focused on MC1DN17/Leigh-like complex I disease with basal ganglia lesions, bilateral striatal necrosis, epilepsy, psychomotor retardation, ataxia, dystonia, and lactic acidosis. The cached IEMbase rows do not describe the Fanconi proximal-tubulopathy phenotype.
Leigh_Syndrome.yaml provides broad neurologic and complex I context, but not
NDUFAF6 disease-level completeness.
Concordance and completeness
Judgement: partial gene-level/pathway coverage only. Do not treat the FRTS5 Fanconi subtype as complete coverage for this IEMbase complex I deficiency row.
The local KB correctly knows that NDUFAF6 can cause complex I deficiency, but the represented phenotype is a specific proximal tubulopathy/fibrosis subtype, whereas IEMbase emphasizes Leigh/striatal-necrosis neurologic disease.
Curation actions
- Keep
Fanconi_Renotubular_Syndrome.yaml#FRTS5as real but partial NDUFAF6 context. - Add or extend NDUFAF6/MC1DN17 coverage if DisMech wants the IEMbase row fully represented.
- Preserve bilateral striatal necrosis, basal ganglia MRI abnormalities, epilepsy, psychomotor retardation, ataxia, dystonia, lactic acidosis, elevated lactate, and decreased complex I activity.
- Do not infer Fanconi syndrome features from this IEMbase row without source review.