Mitochondrial Complex I Deficiency, Nuclear Type 8

A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 8 (MC1DN8) is caused by homozygous or compound heterozygous mutation in the NDUFS3 gene (603846) on chromosome 11p11.

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

Clinical Features

Benit et al. (2004) reported a boy from Reunion Island with complex I deficiency and features of Leigh syndrome (see 256000) caused by mutations in the NDUFS3 gene. The boy's psychomotor development was normal until 9 years of age, although a single episode of febrile convulsions occurred at 9 months of age and kyphoscoliosis had been noted. Persistent stiff neck had developed at the age of 9 years. He gradually developed severe axial dystonia with oral and pharyngeal motor dysfunction, dysphagia, and a tetraparetic syndrome. At 10 years of age, mild elevation of CFS lactate was found. Complex I deficiency was identified by skeletal muscle biopsy. Two years later, he developed acute pancreatitis and severe respiratory insufficiency. He died 1.5 years later after rapid multisystem deterioration.

Haack et al. (2012) reported a patient with encephalopathy, myopathy, developmental delay, and lactic acidosis; Leigh syndrome was not noted.

Molecular Genetics

In a patient with complex I deficiency and features of Leigh syndrome, Benit et al. (2004) identified compound heterozygosity for mutations in the NDUFS3 gene (T145I, 603846.0001 and R199W, 603846.0002).

In a patient with complex I deficiency, Haack et al. (2012) identified homozygosity for the R199W mutation.