Mitochondrial diseases

Abstract

The last two decades have witnessed the discovery of a novel group of inborn metabolic errors which directly impinge upon the pathways of aerobic energy production in the mitochondrial inner membrane and matrix space. The spectrum of reported biochemical abnormalities includes defects which impair the entry of high energy substrates into the mitochondria or the capacity to generate reducing potential from these substrates, as well as those that block the oxidative phosphorylation pathway itself. Clinical expression varies according to the nature, severity and tissue distribution of the metabolic block. Aerobically active organs with a high demand for ATP, such as the brain, retina, cardiac and skeletal muscle, are particularly vulnerable to defects of this type and may be affected either singly or in different combinations. The molecular and genetic mechanisms underlying these disorders have not yet been clearly identified but there are strong theoretical reasons for believing that some of them may be due to mutations affecting the mitochondrial genetic system.