Disorders Of Mitochondrial Oxidative Phosphorylation

A disturbance of oxidative phosphorylation often caused, but not always lactic acidosis, which primarily affects the central nervous system, the retina and the muscles.

See also approach in a patient with suspected congenital metabolic disorder.

A disturbance of oxidative phosphorylation often caused, but not always lactic acidosis, which primarily affects the central nervous system, the retina and the muscles. See also approach in a patient with suspected congenital metabolic disorder. Cellular respiration (oxidative phosphorylation) takes place in the mitochondria. There catalyzes a number of enzymes the transfer of electrons to molecular oxygen and the generation of energy storage ATP. Mitochondrial, nuclear and genetic defects of enzymes involved in this process, interfere with cell respiration and reduce the ratio of ATP to ADP. Tissue with a high energy consumption (for. Example, the brain, nerves, retina, skeletal and cardiac muscle) are particularly vulnerable. Most clinical manifestations include seizures, hypotension, ophthalmoplegia, stroke-like episodes, muscle weakness, severe constipation and a cardiomyopathy. Biochemically, there is a marked lactic acidosis, since the ratio becomes higher NADH to NAD and thereby shifts the equilibrium of the Laktatdehydrogenasereaktion towards lactate. The increase in the lactate / pyruvate ratio is different defects in oxidative phosphorylation of other genetic defects that can cause lactic acidosis, such as the lack of pyruvate carboxylase or pyruvate dehydrogenase, wherein the ratio of lactate: pyruvate remains normal. A large number of defects of oxidative phosphorylation has been described, but only the most common to be mentioned with their specific characters. Mitochondrial mutations and their variants are also blamed for aging processes (eg. As Parkinson’s disease, Alzheimer’s disease, diabetes, deafness and cancer). The following diseases are states with a known phenotype / genotype correlation. Other, less well-defined defects in mitochondrial function exist. In addition, there are a number of conditions under which a genetic defect causes a secondary mitochondrial dysfunction. can happen through adulthood Leber’s hereditary optic neuropathy (LHON) This is a disease with an acute or subacute bilateral central vision due to retinal degeneration that usually begins with 20 to 30 years, but from childhood. The male to female ratio is 4: 1. Many mutations have been identified, but three of them account for 90% of disease in European patients. The LHON- pedigree normally shows a maternal inheritance, as is typical for mitochondrial diseases. Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS syndrome) mutations in the mitochondrial tRNALeu gene cause a progressive neurodegenerative disease that is characterized by repeated episodes of “chemical stroke”, myopathy and lactic acidosis. In many cases, the cells both a wild type and the mutant mitochondrial DNA (heteroplasmy) included; characterized the expression is variable. Myoclonic epilepsy with cracked red fibers (MERRF) This is a progressive disease with uncontrolled muscle contractions (myoclonic seizures), dementia, ataxia, and myopathy (this indicates a mitochondrial proliferation) shows with special stains at biopsy cracked red fibers. The mutations are localized in the mitochondrial gene tRNAlys. A heteroplasia is common and represents a variable expression. Kearns-Sayre syndrome and chronic progressive external ophthalmoplegia (CPEO) These diseases are characterized by a ophthalmoplegia, ptosis, atypical retinitis pigmentosa, red cracked Fasernmyopathie, ataxia, numbness and cardiomyopathy. They typically occur before age 20. Most mutations involve a continuous deletion / duplication process of mitochondrial tRNA and other protein-coding genes. Neurogenic muscular atrophy, retinitis pigmentosa (NARP) and Leigh syndrome Pigmented retinopathy in the presence of a neuromuscular degeneration and Leigh syndrome (subacute necrotizing encephalopathy with ataxia and degeneration of the basal ganglia) are genetically heterogeneous syndromes. The mutations can be found in ATP6 gene of the mitochondrial genome.

Health Life Media Team

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