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Mitochondrial diseases due to disorders of the Krebs cycle
Last reviewed: 23.04.2024
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The main representatives of this group of diseases are mainly associated with deficiency of the following mitochondrial enzymes: fumarase, a-keto-glutarate dehydrogenase complex, succinate dehydrogenase and aconitase.
Mitochondrial diseases of this class have an autosomal recessive type of inheritance. The frequency is not set.
At the heart of pathogenesis is the disruption of the functioning of the tricarboxylic acid cycle, which occupies a central place in the bioenergetic metabolism of cells.
Symptoms. The disease manifests at an early age. In the clinical picture, severe progressive encephalopathy, microcephaly, convulsions, violation of muscle tone are observed. Succinate dehydrogenase deficiency can be characterized by clinical signs resembling Cairns-Seir syndrome (cardiac conduction abnormality, cardiomyopathy, ataxia, visual acuity reduction) or subacute leukemia necrotic encephalomyopathy.
Laboratory research. Biochemical examination of children usually reveals a moderate metabolic acidosis, an increase in the level of lactic acid in the blood, a high renal excretion of the corresponding metabolites of the Krebs cycle. There may be mild hypoglycemia, a slight increase in ammonia in the blood. In fibroblasts and myocytes, a sharp decrease in the activity of the corresponding key enzyme is determined.
Differential diagnosis is aimed at excluding mitochondrial encephalomyopathies caused by an electronic transport defect and oxidative phosphorylation, lactate acidosis, symptomatic epilepsy, and perinatal encephalomyopathy.
Treatment. For stimulation of energy metabolism in the complex treatment using various enzymatic reactions cofactors: coenzyme Q-10 to 60-90 mg / day, vitamin B1, B 2, B 6, nicotinamide 30-60 mg / day, preparations of levocarnitine (25-50 mg / kg daily) for 3-4 months, cytochrome C in 2-4 ml intramuscularly or intravenously (10 injections per course). Recommended frequent feeding with an increase in carbohydrate intake up to 60% of caloric intake. Despite the treatment, its effectiveness requires further research and evidence.
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