Mitochondrial Complex I Deficiency, Nuclear Type 31

A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 31 (MC1DN31) is caused by homozygous mutation in the TIMMDC1 gene (615534) on chromosome 3q13.

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

Clinical Features

Kremer et al. (2017) reported 3 unrelated patients (35791, 66744, and 96687) with mitochondrial complex I deficiency. All patients had severe neurologic dysfunction manifest as infantile-onset hypotonia, failure to thrive, and delayed or minimal psychomotor development. Additional more variable features included sensorineural deafness, dysmetria, dyskinetic movements, peripheral neuropathy, and nystagmus. One patient had brain imaging results consistent with Leigh syndrome, and another patient developed refractory seizures. Two patients died at ages 30 and 20 months; the third patient was alive at age 6 years, but had 2 older sibs who died young from a neurodegenerative disorder with severe epilepsy. The patients, from Greece, Northern Africa, and Germany, were of differing ethnic descent.

Molecular Genetics

In 3 unrelated patients (35791, 66744, and 96687) with mitochondrial complex I deficiency, Kremer et al. (2017) identified a homozygous mutation in the TIMMDC1 gene (615534.0001).