Diagnostic des maladies mitochondriales

Abstract

Mitochondrial diseases, defined as disorders due to a defect in the phosphorylative oxidation chain (OXPHOS), are the most common inherited diseases of metabolism. These diseases have of very large clinical presentation and difficult diagnosis. They are essentially genetic, due to the alteration of very diverse genes located either on the mitochondrial DNA (mtDNA), or on the nuclear genome. Recent technological advances (NGS) with exome sequencing (WES) have allowed the discovery of many new genes and a better understanding of the pathophysiological mechanisms of these diseases. The diagnostic approach is based on the clinical presentation, biochemical explorations, imaging, histopathology and genetics. The genetic investigations concern the entire mtDNA, followed, if negative, by analysis of large panels of nuclear genes. Only the detection of the causal gene allows to affirm the diagnosis of mitochondrial disease ; in the absence of treatment for these diseases, it allows for genetic counseling and the possibility for parents to give birth to unaffected children.