Mitochondrial Complex V (Atp Synthase) Deficiency, Nuclear Type 3

A number sign (#) is used with this entry because of evidence that mitochondrial complex V (ATP synthase) deficiency nuclear type 3 (MC5DN3) is caused by homozygous mutation in the ATP5E gene (ATP5F1E; 606153) on chromosome 20q13. One such patient has been reported.

For a general phenotypic description of the nuclear type of mitochondrial complex V deficiency and a discussion of genetic heterogeneity of mitochondrial complex V deficiency, see 604273.

Clinical Features

Mayr et al. (2010) described a 22-year-old Austrian woman (P3), previously reported by Cizkova et al. (2008), with a history of neonatal-onset lactic acidosis, 3-methylglutaconic aciduria, mild mental retardation, hypertrophic cardiomyopathy, and peripheral neuropathy. Fibroblasts showed a 60 to 70% decrease in both oligomycin-sensitive ATPase activity and mitochondrial ATP synthesis. The mitochondrial content of the ATP synthase complex was equally reduced, but its size was normal.

Molecular Genetics

In an Austrian woman with ATP synthase deficiency in whom mutation in the TMEM70 gene (612418) had been excluded (Cizkova et al., 2008), Mayr et al. (2010) identified a homozygous tyr12-to-cys (Y12C) mutation in the ATP5E gene (606153.0001). The healthy, nonconsanguineous parents were heterozygous for the mutation, which was not found in 180 Austrian control chromosomes.