Mitochondrial Complex I Deficiency, Nuclear Type 32

A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 32 (MC1DN32) is caused by compound heterozygous mutation in the NDUFB8 gene (602140) on chromosome 10q24.

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

Clinical Features

Piekutowska-Abramczuk et al. (2018) reported 2 unrelated children with mitochondrial complex I deficiency. One child presented at 3 months of age with respiratory failure, seizures, and increased serum and CSF lactate. He had hypotonia, failure to thrive, and severely delayed psychomotor development with limited contact with his environment. He also developed left ventricular cardiac hypertrophy. Brain imaging showed signal alterations in the midbrain, putamen, and thalamus, consistent with Leigh syndrome (see 256000) with later development of supratentorial and brainstem atrophy and cystic lesions. The patient was ventilator-dependent and fully dependent for all daily life activities. The other child was born at term and needed immediate resuscitation. He had poor growth, hypotonia, and delayed development. Laboratory studies showed increased serum and CSF lactate and lesions in the basal ganglia and internal capsule, consistent with Leigh syndrome. He died at age 15 months.

Molecular Genetics

In 2 unrelated children with mitochondrial complex I deficiency nuclear type 32 manifest as Leigh syndrome, Piekutowska-Abramczuk et al. (2018) identified compound heterozygous mutations in the NDUFB8 gene (602140.0001-602140.0004). The mutations, which were found by whole-exome or targeted exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families.