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Subacute necrotizing encephalomyopathy Leia
Last reviewed: 23.04.2024
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About the disease was first mentioned in 1951. To date, more than 120 cases have been described. Lei's disease (OMIM 256000) is a genetically heterogeneous disease that can be inherited both by nuclear type (autosomal recessive or linked to the X chromosome) and mitochondrial (less often).
[Causes of the Leia's syndrome
At the heart of the disease is a deficiency of enzymes that provide energy formation mainly due to a disruption in the metabolism of pyruvic acid and a defect in the transport of electrons in the respiratory chain. A deficiency of the pyruvate dehydrogenase complex (a-El subunit), pyruvate carboxylase, complex 1 (NAD-coenzyme Q-reductase) and complex 4 (cytochrome oxidase) of the respiratory chain develops.
It was established that the defects of pyruvate carboxylase, complex 1 (NAD-coenzyme Q-reductase) and complex 4 (cytochrome oxidase) of the respiratory chain are inherited in an autosomal recessive manner, defects of the pyruvate dehydrogenase complex (a-El subunit) are X-linked recessively. At point mutations of mtDNA, which affect the 6th subunit of ATPase, mitochondrial inheritance is characteristic. Most often there is a mutation mutation associated with the replacement of thymine with guanine or cytosine at position 8993 mtDNA. Less common is a mutation at position 9176 mtDNA. Due to the fact that mutation T8993G is the main defect in NARP syndrome, families with the presence of these two diseases are described. Children also have a mutation of mtDNA at position 8344, which occurs in the MERRF syndrome.
It is suggested that in the case of accumulation of mutant mtDNA in the majority of mitochondria a severe course of the Leia syndrome develops. In the mitochondrial genesis of this state, mutant mtDNA is detected in 90% of all mitochondria. Pathogenesis is associated with a violation of energy production in cells and the development of lactic acidosis.
Symptoms of the Leia's syndrome
The first signs of the disease debut at an early age (1-3 years). However, cases of manifestation of the disease in the 2-week and 6-7-year-olds are known. Initially, nonspecific disorders develop: delay in psychomotor development, decreased appetite, episodes of vomiting, and lack of body weight. Subsequently, neurological symptoms increase: muscle hypotension or dystonia with the transition to hypertonia, myoclonic or tonic-clonic convulsions, limb tremor, choreoathetosis, coordination disorder, decreased tendon reflexes, lethargy, drowsiness. Cerebral neurodegeneration has a progressive nature. The symptoms of pyramidal and extrapyramidal insufficiency grow, the swallowing act is broken. Often observe such changes in the organ of vision as ptosis, ophthalmoplegia, atrophy of the optic nerves, less often pigmentary degeneration of the retina. Sometimes hypertrophic cardiomyopathy develops, tachypnea episodes appear.
Rarely, the disease proceeds according to the type of acute encephalopathy. More characteristic is a chronic or subacute current, which leads to a fatal outcome a few years after the onset of the disease. With a rapid flow (several weeks), death occurs as a result of paralysis of the respiratory center.
Diagnostics of the Leia's syndrome
In a biochemical blood test, lactate acidosis is detected due to the accumulation of lactic and pyruvic acids in the blood and liquor, as well as an increase in the content of alanine in the blood. Also, the level of ketone bodies can be increased. In urine, there is an increased excretion of organic acids: lactic, fumaric, etc. The level of carnitine in blood and tissues is often reduced.
EEG results reveal focal signs of epileptic activity. According to MRI data, an expansion of the ventricles of the brain, bilateral brain damage, calcification of the basal ganglia (caudate nucleus, shell, black substance, pale ball) are detected. It is also possible to identify atrophy of the cerebral hemispheres and brain substances.
Morphological examination reveals gross changes in brain substance: symmetrical foci of necrosis, demyelination and spongy degeneration of the brain, mainly of the middle sections, the bridge, subcortical nodes, thalamus, optic nerve. The histological picture includes cystic degeneration of the brain tissue, astrocytic gliosis, death of neurons, an increase in the number of mitochondria in the cells. In skeletal muscles - accumulation of lipid inclusions, a decrease in histochemical response to complexes 1, 4 of the respiratory chain, subarachromolemal accumulation of mitochondria, anomalous mitochondria with disorganization of cristae. The phenomenon of RRF is often not detected.