Mitochondrial disease

Mitochondrial diseases are inherited metabolic diseases caused by mutations either in the nucleus in genes for mitochondrial enzymes or in mitochondrial DNA, which have various clinical manifestations. They are characterized by a specific type of inheritance with significant variability in the manifestation of the disease in offspring. They may relate to the following functions of mitochondria:


 * Oxidative phosphorylation (OXPHOS)
 * Citric Acid Cycle (TCC)
 * β-oxidation
 * Urea cycle – urea cycle disorders
 * Triggering apoptosis



A conservative estimate of the incidence of mitochondrial disease is 11.5 affected per 100,000 population.

The disease manifests itself when 60-90% of mutant mitochondria are present in a given tissue location. However, some mutant mtDNAs have a replication advantage.

Disease associated with mitochondrial fusion and fission disorder
In a normal mitochondrion, fusion and fission of both the outer and inner membranes still occur. Mitofusin proteins with GTPase activity are involved in this.

Charcot-Marie-Tooth
Mutation of the gene for mitofusin 2. Autosomal dominantly inherited optic atrophy.

Disorders in the mitochondrial metabolism of pyruvate and the citrate cycle
It is usually a disease with autosomal recessive inheritance. Enzymopathies occur mainly in:


 * pyruvate dehydrogenase - most often E1 subunit defect, X-linked, lactic acidosis, Leigh syndrome, encephalopathy
 * pyruvate decarboxylase
 * phosphoenolpyruvate carboxykinase
 * fumarase — heterozygotes have a predisposition to leiomyomas of the skin and uterus and to kidney cancer