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December 20, 2016 00:04

Mitochondrial diseases caused by disturbance of pyruvate metabolism

Among the genetically determined pyruvic acid metabolism diseases isolated defects and pyruvate carboxylase pyruvate dehydrogenase complex.Most of these states, with the exception of E deficiency, the alpha component

pyruvate dehydrogenase complex, have an autosomal recessive or linked recessive X-linked inheritance.The population frequency of disease has not been established.

in the pathogenesis of diseases of the main role belongs to the disruption of pyruvate metabolism - the end product of catabolism of carbohydrates and the basic substrate that enters the Krebs cycle.As a result of the enzyme deficiency develop severe disorders associated primarily with the developing lactate and pyruvate acidosis.

clinical picture.There are three main clinical forms: congenital lactic acidosis, subacute necrotizing encephalomyopathies Leia and intermittent ataxia.

Congenital lactic acidosis different early onset in the first weeks or months of a child's life.Develop heavy general condition, seizures, vom

iting, lethargy, respiratory disorders, developmental disorder.

initial signs of subacute necrotizing encephalomyopathies Leia usually appear on the 1-3-year life.The main symptoms include: psychomotor retardation, hypotonia, alternating with dystonia and hypertonia, tonic-clonic and myoclonic seizures, choreoathetosis, tremor of the extremities, koordinatornye disorder, lethargy, somnolence, respiratory distress syndrome, optic atrophy, sometimes ptosis, ophthalmoplegia.The course progresses.Typical violations noted during magnetic resonance imaging study of the brain in the form of bilateral symmetrical lesions, including basal ganglia calcification (shell, the caudate nucleus, substantia nigra, globus pallidus), as well as atrophy of the cerebral cortex and the brain substance.At post mortem examination reveals symmetric area of ​​necrosis, demyelination and spongiform degeneration in the midbrain, the bridge, the basal ganglia, thalamus, optic nerve.

Intermittent ataxia has a relatively late onset and benign course.

Laboratory studies.Basic biochemical changes - metabolic acidosis, and giperlaktat- giperpiruvatatsidemiya.

Differential diagnosis.The phenotypic manifestations of pyruvate metabolic diseases caused by defects in the pyruvate dehydrogenase complex or pyruvate, are similar.To confirm the diagnosis study shows the activity of these enzymes in leukocytes or fibroblasts.In the differential diagnosis should be borne in mind that congenital lactic acidosis and subacute necrotizing encephalomyopathies Leia are genetically heterogeneous clinical phenotypes and may be associated with a variety of hereditary defects, in particular, these conditions may be the result of an autosomal recessive or mitochondrial inherited deficiency of complexes 1,4 and 5 of the respiratory chain.Detection of patients with these defects is fundamentally changing the tactics of treatment and medical-genetic prognosis.

treatment.Complex treatment of children suffering from diseases of pyruvate metabolism include:

  • appointment of vitamins and cofactors, enzyme systems involved in the metabolism of pyruvic acid (thiamine 50-100 mg / day, thioctic acid 100-500 mg / day, 5-10 mg of biotin /d) dimephosphone 90 mg / kg per day.
  • dietary treatment, which is necessary to fill the growing shortage of acetyl-CoA.Assign ketogenic diet, which provides up to 75% of the energy needs at the expense of revenue fat, up to 15% - of protein and only 10% - carbohydrates.Information about the effectiveness of complex treatment of patients with pyruvate metabolism defects contradictory.