Les déficits de la chaîne respiratoire : démarche diagnostique des cytopathies mitochondriales

Mitochondria, the “powerhouse” of the cell, are at the crossroads of carbohydrate, lipid and protein metabolisms. The respiratory chain (RC) plays a central role by performing oxidative phosphorylation that is oxygen consumption coupled with ATP synthesis. The inherited defects of RC itself or of all the processes involved in its functioning are called “mitochondrial disorders”. These diseases can be inherited maternally (mitochondrial DNA mutation) or by mendelian patterns (mutation on one of the many nuclear genes involved in mitochondrial bioenergetics). The clinical presentation of the mitochondrial disorders is highly various and numerous differential diagnoses must be considered. The diagnostic approach therefore looks for biochemical arguments to direct or support molecular analysis. Signs of blockage of energetic metabolism (hyper-lactacidemia, paradoxical ketonemia...) will be first sought by global screening tests. Specific functional studies of RC (enzymatic activities and oxygen consumption in particular) and analysis of the integrity and the quantity of mitochondrial DNA in different tissues will then provide more direct evidence. The diagnosis of mitochondrial disorder, however, can only be confirmed by the identification of a proven deleterious variant.