Mitochondria have an essential role in maintaining cellular homeostasis, and their many functions integrate closely with the cellular metabolic network. It is therefore naive to think of mitochondria in isolation, and although we recognise primary disorders of mitochondrial function, the cellular and clinical consequences will depend on many other genetic and environmental factors. Precisely how the jigsaw fits together will vary from person to person. This presents a unique challenge to neurologists wanting to identify, diagnose, and manage patients and families with mitochondrial disease. In this respect, areas for future development are highlighted in box 1.
These are not rare disorders. Recent epidemiological studies have shown that as a group primary mitochondrial disorders affect at least one in 8000 of the general population,95 and that number is likely to increase as the genotypic and phenotypic spectrum expands. It is also becoming clear that mitochondrial dysfunction occurs in many common sporadic neurological disorders, and there may be common mitochondrial mechanisms associated with certain neurological phenotypes (a good example being the various forms of hereditary spastic paraplegia). Our grasp of primary mitochondrial disorders will therefore have a much broader relevance, helping us to understand many other diseases and hopefully leading to novel generic treatments for neurological diseases.