Mitochondrial Complex I Deficiency, Nuclear Type 28

A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 28 (MC1DN28) is caused by homozygous mutation in the NDUFA13 gene (609435) on chromosome 19p13. One such family has been reported.

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

Clinical Features

Angebault et al. (2015) reported 2 sisters, born of consanguineous Turkish parents, with mitochondrial complex I deficiency. The girls had onset of symptoms in infancy after a normal neonatal period; they presented with delayed development, hypotonia, poor eye contact, abnormal eye movements, and failure to thrive in 1. The disease course was consistent with complex I deficiency manifest as slowly progressive encephalopathy with dyskinesia, abnormal movements, hearing loss due to auditory neuropathy, severe optic neuropathy with retinal dysfunction, pyramidal tract signs, and lactic acidosis, without extraneurologic involvement. One patient had well-controlled seizures. Brain imaging in 1 patient was normal until age 7 years, when progressive cerebellar atrophy was noted. The patients were still alive at ages 12 and 5 years, although handicapped. Angebault et al. (2015) noted the slow progression of the disorder in this family.

Molecular Genetics

In 2 sisters, born of consanguineous Turkish parents, with mitochondrial complex I deficiency, Angebault et al. (2015) identified a homozygous missense mutation in the NDUFA13 gene (R57H; 609435.0002). (The authors referred to the mutation as R47H in parts of the report.) The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases, or in 100 control individuals.