Mitochondrial Complex I Deficiency, Nuclear Type 6

A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 6 (MC1DN6) is caused by homozygous mutation in the NDUFS2 gene (602985) on chromosome 1q23.

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

Clinical Features

Loeffen et al. (2001) reported 3 unrelated families with isolated complex I deficiency. The first family, which was consanguineous, had 2 affected children. The first affected child, a male, was normal until 6 months of age when he manifested neurologic regression, with horizontal nystagmus and bilateral muscle atrophy with decreased axial muscle tone. Brain CT showed bilateral hypodensities of the basal ganglia, and echocardiogram showed left ventricular hypertrophy. He died of apnea at 24 months of age. The third-born child, a female, had similar symptoms except that they presented earlier and her deterioration was faster. In the second family, the affected child had neonatal onset of severe lactic acidosis and hypertrophic cardiomyopathy. She died at 4 days of age. The third family, which was consanguineous, had 4 children, 3 of whom died with a clinical phenotype including failure to thrive, horizontal nystagmus, ataxia, hypotonia, and pallor of the optic discs. CT and MRI findings revealed hypodensity of the basal ganglia and midbrain.

Clinical Management

Bar-Meir et al. (2001) studied the effects of agents commonly used in the treatment of mitochondrial complex I deficiency in fibroblasts from a patient with a homozygous mutation in the NDUFS2 gene (602985.0001). They observed marked improvement with riboflavin, which nearly normalized the ATP production.

Molecular Genetics

In patients with isolated complex I deficiency, Loeffen et al. (2001) identified homozygosity for 3 different missense mutations in the NDUFS2 gene (602985.0001-602985.0003).