Mitochondrial Diseases

Abstract

Mitochondrial diseases (prevalence 1:5,000) represent a heterogeneous group of multisystemic disorders which often affects skeletal muscle and nervous system and is mostly due to dysfunction of the mitochondrial respiratory chain. The tissues with the highest energy expenditure are the most vulnerable. The disorders are caused either by mutations of mtDNA, or nDNA. A special group of the mitochondrial disorders is the defect of intergenomic communication disturbancy which affects the mtDNA quantitatively (mtDNA depletion) or qualitatively (multiple mtDNA deletion). Owing to the unequal distribution of mitochondria in the different tissues and the co-existence of mutant and wild type mtDNA, these disorders may present with a huge variety of symptoms, making diagnosis difficult. In every year about ten new disease-causing genes are discovered. In the diagnosis of the mitochondrial disorders the muscle histology and the molecular biology play the most important role. Identification of the disease causing mutations may help to select the most effective therapy. E.g. ketogenic diet is effective mostly in pyruvate dehydrogenase deficiency, valproate should be avoided in cases with special SNPs in the POLG1 gene. In summary: the molecular stratification of the mitochondrial disorders is very important in the predictive and preventive treatment of this rare disease group.