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IEMbase 0681: NDUFAF5-related complex I assembly factor 5 deficiency

Scope

Field Value
IEMbase ID 681
Nosology 7.1.05.01
Nosology code IEM0441
Gene NDUFAF5
External IDs OMIM:618238; ORPHA:255241
Generated mapping CANDIDATE to COX4I1-Related_COX_Deficiency.yaml
Candidate DisMech targets Broad complex I/Leigh context only; no exact NDUFAF5 target
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents autosomal recessive NDUFAF5-related complex I assembly factor 5 deficiency, also labeled mitochondrial complex I deficiency, nuclear type 16.

Biochemical rows include decreased fibroblast complex I activity across all ages, increased plasma lactate across all ages, and increased CSF lactate in the neonatal and infantile periods. Clinical rows are broad: basal ganglia MRI abnormalities, Leigh syndrome, lactic acidosis, hypotonia, dystonia, spasticity, epilepsy or seizures, choreoathetosis, extrapyramidal signs, movement disorder, intellectual disability, failure to thrive, brain MRI abnormality, and multiple dysmorphology/developmental prompts including micrognathia, small chin, small mouth, abnormal toes, facial dysmorphism, hair abnormality, intrauterine growth retardation, and small sacral pit.

DisMech phenotype coverage

No exact NDUFAF5 or MC1DN16 target was identified.

Leigh_Syndrome.yaml covers much of the shared syndrome-level neurologic package, including complex I deficiency, lactic acidosis, hypotonia, basal-ganglia involvement, dystonia/movement disorder, ataxia, seizures, and failure to thrive. It does not cover the NDUFAF5 entity or the detailed dysmorphology and congenital-anomaly prompts in this row.

The generated COX4I1-Related_COX_Deficiency.yaml candidate is a complex IV deficiency and should not be accepted for a complex I assembly factor.

Concordance and completeness

Judgement: true local gap with substantial broad Leigh overlap.

If curated, this record needs a gene-specific NDUFAF5 disease model rather than being folded into generic Leigh syndrome. The non-Leigh detail in IEMbase is important: facial/hair/toe findings, intrauterine growth retardation, sacral pit, CSF lactate, choreoathetosis, and age-banded neurologic progression.

Curation actions

  • Add a dedicated NDUFAF5/MC1DN16 target if curated.
  • Reject COX4I1-related complex IV deficiency as exact coverage.
  • Preserve decreased complex I activity, plasma and CSF lactate, basal-ganglia MRI abnormalities, Leigh syndrome, movement disorder, seizures/epilepsy, spasticity, intellectual disability, and dysmorphology prompts.
  • Use Leigh_Syndrome.yaml only for shared syndrome context.