Mitochondrial Complex I Deficiency, Nuclear Type 18

A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 18 (MC1DN18) is caused by homozygous or compound heterozygous mutation in the NDUFAF3 gene (612911) on chromosome 3p21.

For a discussion of genetic heterogeneity of mitochondrial complex I deficiency, see 252010.

Clinical Features

Saada et al. (2009) reported 5 patients from 3 families with severe complex I deficiency. All patients died by age 6 months. Three sibs in the first family presented similarly with severe lactic acidosis. In a second family, the infant was hypoactive, sucked poorly, had macrocephaly, a weak cry, wide anterior fontanel, and axial hypotonia. He also had intermittent tonic movements and pallor of the optic discs. At 3 months of age, there was no eye contact and marked axial hypotonia with brisk tendon reflexes. In the third family, a daughter of unrelated parents of Jewish origin was affected. She developed myoclonic seizures at age 3 months, and brain MRI revealed diffuse brain leukomalacia. She died at age 6 months of respiratory failure. Complex I activity was decreased in cells derived from all patients.

Molecular Genetics

Saada et al. (2009) identified homozygous or compound heterozygous mutations in the NDUFAF3 gene (612911.0001-612911.0003) in 5 patients with severe complex I deficiency.