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.

Keywords

Oxidative phosphorylation - mitochondrial DNA - Kearns-Sayre syndrome - chronic progressive external ophthalmoplegia - myoclonic epilepsy and ragged red fiber disease - mitochondrial encephalomyopathy - lactic acidosis - and stroke-like episodes (MELAS) - Leigh disease - Leber hereditary optic neuropathy - cerebellar ataxia - mtDNA depletion - myoneurogastrointestinal disorder and encephalopathy (MNGIE) - Wolfram syndrome - hereditary spastic paraplegia with ragged-red fiber myopathy - Friedreich ataxia - Wilson disease