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Mitochondrial Disordes

A summarizing overview with links to further detailed information.

Mitochondria are the semiautonous power stations of the cell. They have their own genome (mtDNA), which codes besides the nuclear genome in part for their proteins. Mitochondrially coded proteins are also mitochondrially transcribed, translated and synthesized. There are additionally important metabolic pathways located within these organelles: the ß-oxidation and the carnitin-dependent transmembranal transport of fatty acids, the Krebs cycle and the oxidative phosphorylation; they all contribute to the energy production which is essential for the vitality of the cell. The huge variation of mitochondrial disorders is due to the different mode and localisation of the causative gene defects, as well as their variable, tissue specific manifestation. The term “mitochondrial disorders” is focused in a more reduced way on the clinical manifestations caused by structural and functional disturbances of the mitochondrially localized oxidative phosphorylation.

Manifestations during the childhood mostly result in severe forms (rapid progressive system disorders, primarily with involvement of the brain and the muscle) sometimes with a bad prognosis (seizures, "floppy infants", fatal infantile myopathies and cardiomyopathies). Later manifestations are ophthalmologic, neuromuscular and neuroendocrine disorders like Leber’s hereditary opticus neuropathie, chron. progredient extern 0phthalmoplegia, Friedreich’s ataxia, cardiomyopathie, Diabetes mellitus; a causative effect for M. Parkinson is in discussion. Mitochondrial metabolic defects are also thought to be responsible for ageing.

The causative gene defects include sporadic and pure maternally inherited point and length mutations as well as autosomal dominant and recessively inherited mutations in the nuclear genome. It is in discussion also, that mutations within the mtDNA contribute to polygenic disorders with a complicated mode of inheritance.

Specificitic features of these disorders are the variant clinical manifestion, the complex diagnostics and the reduced therapeutical options. Most likely a relevant part of the causative gene defects are not identified yet.