Mitochondrial Complex I Deficiency, Nuclear Type 22

A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 22 (MC1DN22) is caused by homozygous or compound heterozygous mutation in the NDUFA10 gene (603835) on chromosome 2q37.

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

Clinical Features

Hoefs et al. (2011) reported a boy with mitochondrial complex I deficiency nuclear type 22 manifesting as Leigh syndrome (see 256000). The patient showed delayed psychomotor development after a normal neonatal period, hypotonia, increased serum and CSF lactate, periods of abnormal breathing, and hypertrophic cardiomyopathy. Brain MRI showed symmetric lesions in the basal ganglia. He died at age 23 months from respiratory arrest and cardiac decompensation. Laboratory studies showed severely reduced complex I activity, at 29% and 7% of normal in fibroblasts and muscle tissue, respectively, and Western blot analysis showed decreased NDUFA10 protein. In addition, complex III activity was reduced to 68% of controls. There was a decreased amount of fully assembled complex I, although subcomplexes 4 and 6 were present. These findings indicated that NDUFA10 is incorporated into complex I during the late assembly stages.

Kohda et al. (2016) reported a male infant (patient 057) with mitochondrial complex I deficiency who presented with intrauterine growth retardation, lactic acidosis, and pulmonary hypertension. Brain imaging was not reported.

Molecular Genetics

In a boy mitochondrial complex I deficiency manifesting as Leigh syndrome, Hoefs et al. (2011) identified compound heterozygosity for 2 mutations in the NDUFA10 gene: M1V, 603835.0001 and Q142R (603835.0002). Each mutation was inherited from an unaffected parent, and neither mutation was found in 108 controls.

In a male infant (patient 057) with MC1DN22, Kohda et al. (2016) identified compound heterozygous mutations in the NDUFA10 gene: (L294P, 603835.0003 and a 3-bp insertion, 603835.0004).