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We present the clinical case of patient with epilepsy, developmental retardation and hearing loss. The whole exome sequencing allowed to reveal compound heterozygous variants of the nucleotide sequence in SPATA5 gene (c.1714+1G>A, c.1678G>A). Mutations in the SPATA5 gene have been described in patients with epilepsy, hearing loss and mental retardation syndrome (MIM 616577). Paired parents were carriers of one heterozygous gene variant. Such mutations lead to the development of epileptic disorders in 3% of cases, and should be considered in patients not only as a possible cause of neurodegenerative diseases, but also leading to pathology with clinical manifestations mimicking mitochondrial disease.

This lecture with a description of clinical cases presents information on such a mitochondrial disease from the group of hereditary metabolic diseases, like MELAS syndrome (OMIM: 540000). The main manifestations of this progressive disease are stroke-like episodes and a specific form of encephalopathy, including epileptic seizures with the presence of a phenomenon of "ragged red fibers" and early dementia. Clinical cases, given in this lecture, supplement the piggy bank of genetically verified mitochondrial diseases leading to the development of polymorphic neurological disorders and characteristic neuroimaging picture, namely the appearance of polymorphic ischemic changes in the temporal, parietal or occipital regions of the brain, that do not correspond to the zones of the main vascular blood supply, as the basis for the formation of such focus is the phenomenon of mitochondrial angiopathy, and not thrombosis. The description of clinical cases reflects our own observations and the main steps in the diagnosis of this severe hereditary disease, taking into account of the latest neurogenetic representations. In addition to the data given in the clinical course of the disease, the results of the genetic interpretation of the MELAS syndrome are given; modern methods of diagnosis and therapy are considered.

The article presents current views on energy metabolism in a living cell, information on the mechanisms of its implementation in norm and in pathology. The methods of diagnostics of intracellular energy disturbances including the assessment of mitochondrial enzymes activity in blood lymphocytes, the level of total and bound carnitine using photoelectrocolorimetry and liquid tandem chromatomass spectrometry methods are discussed in detail. The main clinical manifestations of mitochondrial disorders are described: pathological manifestations on the part of the muscular and central nervous systems, the heart, other somatic organs, the polysystemic nature of lesions. The authors analyze the recent medical publications on the state of energy metabolism in different pathologies in children: with mitochondrial diseases, pathology of the digestive tract, urinary system, vegetovascular dystonia, etc. Data on the ways of correction of energy metabolism disorders using the energy-rich therapy are presented. It is convincingly shown that mitochondrial disorders require L-carnitine preparations in the form of monotherapy or in combination with other drugs.

Systems biology analysis of over 700 magnesium-dependent proteins in human proteome shown that these proteins affect (1) the embryonic development, (2) energy metabolism, (3) signal transduction processes from receptors, (4) neurological function, (5) support of connective tissue structure, (6) cardiovascular and (7) immunological roles. Magnesium deficiency during pregnancy will stimulate development of congential malformations (skeletal defects, rickets, hernia of the diaphragm, facial defects, craniosynostosis, structural disorders of the retina and vision, brachydactyly). Magnesium deficiency at an early age is associated with sudden death syndrome in preschool and adolescence leads to impaired function of skeletal muscles and myocardium. Magnesium deficiency is also characterized by mitochondrial disorders, hyperinsulinemia, disorders of the skin structure and its appendages, tumors and diseases associated with impaired energy metabolism (including hypoparathyroidism and anemia). Effects of magnesium deficiency in children significantly heavier on the background of lack of vitamin B6 (pyridoxine). The results of proteomic analysis enable to point out the relevant molecular and physiological mechanisms of synergy between magnesium and pyridoxine. Overall, the results of the analysis indicate a very extensive area for the correction of magnesium and pyridoxine deficiency for the prevention and treatment of a wide range of diseases, from the period of fetal development and early childhood through adolescence.

Mitochondrial diseases in children are one of the most important interdisciplinary problems in modern pediatrics. The diseases of this group occur due to mutations in nuclear and/or mitochondrial DNA and are manifested by a brain, heart and skeletal muscle lesion (encephalocardiomyopathy). The authors describe a clinical case of NARP (neuropathy, ataxia, retinitis pigmentosa) syndrome in a baby during the first year of life. Early onset in the presence of complete health, the polymorphism of clinical manifestations, such as a central nervous system lesion, muscle weakness, impaired psychomotor development, and seizures, aroused suspicion of the mitochondrial disease; however, the final diagnosis was established by molecular genetic testing. The m8993T>G mutation was found in the MT-ATP6 gene, which confirmed the mitochondrial disease NARP syndrome. The description of the clinical case of the mitochondrial disease in a baby during the first year of life is of real interest to neurologists and pediatricians. Signs, such as the appearance or worsening of initially existing developmental delay in the early period of life, addition of muscle hypotonia with a change in the reflex areas, loss of acquired skills, impaired vision and hearing, and the progressive nature of the disease, may be indicative of the mitochondrial disease and the need to exclude diseases of this group by specific studies, including molecular genetic testing.

The paper considers the problem of diagnosing the heterogeneous forms of mitochondrial cardiomyopathies associated with impaired oxidative phosphorylation and decreased activity of the mitochondrial electron transport system due to mutations in mitochondrial or nuclear DNA genes. It is emphasized that mitochondrial cardiomyopathies rarely present as an isolated myocardial lesion and more frequently serve as a manifestation of multisystem disease. The paper provides the characteristics of cardiomyopathies in some mitochondrial syndromes and shows the possibilities of treating this disease.

The article is on some contemporary data about genetic specifics of patients with sleep apnea syndrome. The data discussed is concerned on either adult and newborn subjects with the syndrome.

It is suggested that mitochondrial diseases might be identified in 22—33% of cryptogenic stroke cases in young subjects. The incidence of mitochondrial disorders in patients with stroke is unknown; it is 0.8 to 7.2% according to the data of some authors. The paper gives data on the prevalence, pathogenesis, and clinical manifestations of mitochondrial diseases, such as mitochondrial encephalopathy, lactic acidosis, and stroke-like syndrome (MELAS) and insulin-like episodes; myoclonic epilepsy and ragged-red fibers (MERRF) syndrome, and Kearns-Sayre syndrome (sporadic multisystem mitochondrial pathology).