Mitochondrial diseases are a group of genetic disorders that are characterized by defects in oxidative phosphorylation and caused by mutations in genes in the nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) that encode structural mitochondrial proteins or proteins involved in mitochondrial function. Mitochondrial diseases are the most common group of inherited metabolic disorders and are among the most common forms of inherited neurological disorders. One of the challenges of mitochondrial diseases is the marked clinical variation seen in patients, which can delay diagnosis. However, advances in next-generation sequencing techniques have substantially improved diagnosis, particularly in children. Establishing a genetic diagnosis allows patients with mitochondrial diseases to have reproductive options, but this is more challenging for women with pathogenetic mtDNA mutations that are strictly maternally inherited. Recent advances in in vitro fertilization techniques, including mitochondrial donation, will offer a better reproductive choice for these women in the future. The treatment of patients with mitochondrial diseases remains a challenge, but guidelines are available to manage the complications of disease. Moreover, an increasing number of therapeutic options are being considered, and with the development of large cohorts of patients and biomarkers, several clinical trials are in progress.

ObjectiveThe prevalence of mitochondrial disease has proven difficult to establish, predominantly as a result of clinical and genetic heterogeneity. The phenotypic spectrum of mitochondrial disease has expanded significantly since the original reports that associated classic clinical syndromes with mitochondrial DNA (mtDNA) rearrangements and point mutations. The revolution in genetic technologies has allowed interrogation of the nuclear genome in a manner that has dramatically improved the diagnosis of mitochondrial disorders. We comprehensively assessed the prevalence of all forms of adult mitochondrial disease to include pathogenic mutations in both nuclear and mtDNA.MethodsAdults with suspected mitochondrial disease in the North East of England were referred to a single neurology center from 1990 to 2014. For the midyear period of 2011, we evaluated the minimum prevalence of symptomatic nuclear DNA mutations and symptomatic and asymptomatic mtDNA mutations causing mitochondrial diseases.ResultsThe minimum prevalence rate for mtDNA mutations was 1 in 5,000 (20 per 100,000), comparable with our previously published prevalence rates. In this population, nuclear mutations were responsible for clinically overt adult mitochondrial disease in 2.9 per 100,000 adults.InterpretationCombined, our data confirm that the total prevalence of adult mitochondrial disease, including pathogenic mutations of both the mitochondrial and nuclear genomes (≈1 in 4,300), is among the commonest adult forms of inherited neurological disorders. These figures hold important implications for the evaluation of interventions, provision of evidence‐based health policies, and planning of future services. Ann Neurol 2015 Ann Neurol 2015;77:753–759