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Mitochondrial diseases due to disorders of the Krebs cycle
Medical expert of the article
Last reviewed: 07.07.2025
The main representatives of this group of diseases are mainly associated with a 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 has not been established.
The pathogenesis is based on a disorder in the functioning of the tricarboxylic acid cycle, which occupies a central place in the bioenergetic metabolism of cells.
Symptoms. The disease manifests itself at an early age. The clinical picture includes severe progressive encephalopathy, microcephaly, seizures, and impaired muscle tone. Succinate dehydrogenase deficiency may be characterized by clinical signs resembling Kearns-Sayre syndrome (cardiac conduction disorder, cardiomyopathy, ataxia, decreased visual acuity) or manifest as subacute necrotizing encephalomyopathy of Leigh.
Laboratory tests. Biochemical examination of children usually reveals moderate metabolic acidosis, increased blood lactic acid levels, and high renal excretion of the corresponding Krebs cycle metabolites. Mild hypoglycemia and a slight increase in blood ammonia levels may be observed. A sharp decrease in the activity of the corresponding key enzyme is determined in fibroblasts and myocytes.
Differential diagnostics is aimed at excluding mitochondrial encephalomyopathies caused by defects in electron transport and oxidative phosphorylation, lactic acidosis, symptomatic epilepsy, and perinatal encephalomyopathies.
Treatment. To stimulate energy metabolism, various cofactors of enzyme reactions are used in the treatment complex: coenzyme Q-10 at 60-90 mg/day, vitamins B1, B2 , B6 , nicotinamide at 30-60 mg/day, levocarnitine preparations (25-50 mg/kg per day) for 3-4 months, cytochrome C at 2-4 ml intramuscularly or intravenously (10 injections per course). Frequent feeding with an increase in carbohydrate consumption to 60% of the caloric content of the diet is recommended. Despite the treatment, its effectiveness requires further research and evidence.
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What tests are needed?