Purpose of review: The clinical and genetic heterogeneity of mitochondrial myopathies presents considerable diagnostic challenges. In addition, mitochondrial dysfunction seems to contribute to the development and progression of many age-related neurodegenerative diseases. This review presents recently published data concerning prevalence, phenotype, gene discovery, disease mechanisms, diagnostic tools and treatment strategies for mitochondrial diseases, and summarizes current understanding concerning the role mitochondria play in the pathogenesis of other common neurological disorders.
Recent findings: Heteroplasmic levels of pathogenic mitochondrial DNA mutations are common amongst the general population, although there is considerable geographic variation. Mitochondrial abnormalities also occur in common neurodegenerative disorders, implying a mechanistic link between mitochondrial dysfunction and development or progression of disease. The phenotypic spectrum associated with well recognized pathogenic variants continues to expand, whereas next-generation sequencing is identifying new disease-causing nuclear genetic mutations. Biomarkers and imaging modalities for diagnosis and disease monitoring are now in place and novel treatment strategies are emerging. Alas, no clinical trial data for treatment in mitochondrial disease have been published in the last 12 months.
Summary: Despite rapid advances in gene discovery, details concerning the altered protein products and cellular pathways that result in mitochondrial disease remain elusive. Understanding the consequences of deleterious mutations and the cellular adaptive response is imperative so that therapeutic targets can be identified.