Mitochondrial genetic diseases

Mitochondrial diseases are individually uncommon, but collectively pose a significant burden on human health. Primary mitochondrial disease is caused by defects in the mitochondrial DNA-encoded genes or in nuclear genes whose products are imported into the mitochondrion. Great strides have been made in determining the cause of mitochondrial disorders, but the clinical ability to diagnose these conditions lags behind because of phenotypic overlap between distinct genetic entities and the complexity and invasiveness of standard diagnostic testing. In this review, we evaluate new findings in mitochondrial genetics, recent developments in mitochondrial disease diagnostic testing, and emerging ideas for mitochondrial disease therapies.

Clinical cohort studies have revealed important themes in patient care relative to manifestations of mitochondrial disease. Significant strides have also been made toward creating embryos free from the risk of maternally inherited mitochondrial DNA-based disease. Several new genetic causes of both nuclear and mitochondrial DNA-based diseases have been identified in the past year. In addition, novel insights have emerged from basic studies of mitochondrial biology that hold promise for the development of targeted mitochondrial disease therapies.

Research on mitochondrial biology and disease continues to improve the clinical capacity to diagnose the heterogeneous group of mitochondrial diseases that afflict the pediatric population. This research also provides a framework for future approaches to devise effective mitochondrial disease therapies.