Prevalence of nuclear and mitochondrial <scp>DNA</scp> mutations related to adult mitochondrial disease

TLDR

Mitochondrial disease prevalence is hard to determine because of clinical and genetic heterogeneity, but advances in genetic testing have expanded the phenotypic spectrum and improved diagnosis. The study aimed to determine the prevalence of all adult mitochondrial disease forms, including nuclear and mtDNA mutations, in a North East England cohort from 1990 to 2014. The authors calculated minimum prevalence rates in 2011 by assessing symptomatic nuclear DNA mutations and both symptomatic and asymptomatic mtDNA mutations, finding a 1 in 5,000 rate for mtDNA mutations. Nuclear mutations accounted for 2.9 per 100,000 adults, and the overall prevalence of adult mitochondrial disease was about 1 in 4,300, underscoring the need for evidence‑based policies and service planning.

Abstract

The 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.Adults 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.The 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.Combined, 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.