Oxidative Phosphorylation Disease Diagnosis

ABSTRACT Although the mitochondrial (mtDNA) encodes only 13 polypeptide subunits of the oxidative phosphorylation (OXPHOS) enzymes, approximately 1,000 proteins are estimated to be necessary for proper OXPHOS function. Over the past ten years, a wide variety of adult and pediatric OXPHOS diseases were found to be caused by or associated with mtDNA mutations and nuclear DNA mutations. These advances enhanced the ability to definitively diagnose patients, develop management plans, and provide genetic counseling. However, in most individuals, diagnosing OXPHOS diseases is difficult and depends on assessing complex data derived from clinical, neuroradiologic, metabolic, biochemical, and pathologic evaluations. As understanding of nuclear OXPHOS genes grows, a more coherent approach to diagnosis, management, and treatment is likely to emerge. This article reviews major classes of OXPHOS diseases, a diagnostic algorithm, and recent advances in this complex field.