Mitochondrial cytopathies and neuromuscular disorders

In the last decade, mitochondrial diseases were shown not to be rare but to represent an important group of metabolic disorders. Defects are caused by mutations either located in nuclear genes or in mitochondrial genes. Nuclear gene defects are found in complex IV deficient and complex I deficient patients. Deficiencies of complex II are extremely rare. Different phenotypes are associated with complex IV deficiency, including a neonatal form, cardio-encephalomyopathy in young infants, Leigh syndrome, and pure myopathy. Mutations can be found in the complex IV assembly genes, such as the SURF-1 gene and the SCO2 gene. Different phenotypes are also found in complex I deficient patients and include a neonatal form, Leigh syndrome, pure myopathy, pure cardiomyopathy or multiple-system involvement. In some disorders, the mitochondrial DNA abnormalities are caused by a nuclear gene defect (Alpers-Huttenlocher syndrome, autosomal dominant multiple mitochondrial DNA deletion syndrome, and MNGIE syndrome). Since 1988, more then 70 different mutations were reported in the mitochondrial DNA. Some point mutations are associated with a specific phenotype, others have a wide range of clinical symptoms. We expect that many more mitochondrial DNA mutations will be identified in the future. The number of mutations in nuclear genes will also increase, especially since progress has been made in techniques used for identification of nuclear genes (microcell transfer).