Mitochondrial Disease: Advances in clinical diagnosis, management, therapeutic development, and preventative strategies.

Purpose of review: Primary mitochondrial disease encompasses an impressive range of inherited energy deficiency disorders having highly variable molecular etiologies as well as clinical onset, severity, progression, and response to therapies of multi-system manifestations. Significant progress has been made in primary mitochondrial disease diagnostic approaches, clinical management, therapeutic options, and preventative strategies that are tailored to major mitochondrial disease phenotypes and subclasses.

Recent findings: The extensive phenotypic pleiotropy of individual mitochondrial diseases from an organ-based perspective is reviewed. Improved consensus on standards for mitochondrial disease patient care are being complemented by emerging therapies that target specific molecular subtypes of mitochondrial disease. Reproductive counseling options now include preimplantation genetic diagnosis at the time of in vitro fertilization for familial mutations in nuclear genes and some mtDNA disorders. Mitochondrial replacement technologies have promise for some mtDNA disorders, although practical and societal challenges remain to allow their further research analyses and clinical utilization.

Summary: A dramatic increase has occurred in recent years in the recognition, understanding, treatment options, and preventative strategies for primary mitochondrial disease.