Currently, about million new cases of liver cancer (LC) are being registered annually in the world, causing death in 85 % of patients.The purpose of the study is to establish the features of changes in biochemical blood parameters in RP against the background of persistence of DNA/RNA viruses.Patients (n = 247) with morphologically established liver cancer, hepatitis and healthy individuals were examined. The subject of research was the biochemical and molecular biological parameters of DNA/RNA viruses. It was established that the nature of biochemical changes and disorders in patients with liver cancer indicates a simultaneous violation of most physiological functions of parenchymal organs, in which syndromes of cytolysis, cholestasis, immune and autoimmune disorders are simultaneously formed, the main role in which belongs to infectious (DNA/RNA viruses) and oncological processes. The most important biochemical markers in liver cancer are enzymes (AST, ALT, ALP, LDH, alpha-amylase), bilirubin, creatinine, albumin, triglycerides, GGTP, microelements (biogenic – magnesium, phosphorus, calcium). Among the viruses detected during liver cancer, the leading role belongs to viruses verified in tumor tissue, the presence of which causes persistent biochemical changes: VEB and HHV6.

Objectives. To study the methylation profile of the FXN gene and its influence on the formation of the clinical presentation of Friedreich’s disease (FD). Materials and methods. The promoter area and intron 1 of the FXN gene up to the GAA expansion (UP-GAA) and after the GAA expansion (DOWN-GAA) regions were studied in 17 patients with FD, with analysis of a total of 45 CpG sites. Results. Studies of genetic-epigenetic interactions identified correlations between the extent of methylation of a series of CpG sites in the UP-GAA and DOWN-GAA and the number of GAA repeats in both expanded alleles of the FXN gene in patients with FD. We also found a link between methylation and the presence of the extraneural signs of FD: cardiomyopathy was more likely to be present when the CpG site of the promoter region was hypermethylated, while impairments to carbohydrate metabolism were more common in hypomethylation of CpG sites in the DOWN-GAA area. Conclusions. The data obtained here provide evidence that epigenetic modifications of the FXN gene make a significant contribution to forming the clinical picture of FD.

AIM:To develop a complex algorithm for autosomal recessive ataxia (ARA) diagnosis applicable for Russian patients with degenerative ataxias.MATERIAL AND METHODS:48 patients with of presumably degenerative ataxias were examined. Clinical evaluation was performed with the use of the SARA and ICARS scales (for ataxia) and MoCA (cognitive functions), and a set of laboratory tests was carried out, including electromyography, brain MRI, and DNA analysis of mutations responsible for Friedreich's disease and spinocerebellar ataxias (SCAs) types 1, 2, 3, 6 and 17. 28 patients underwent mutation screening using a multigenic MPS panel.RESULTS:8 patients (16.7%) with non-hereditary causes of ataxia were identified: cerebellar alcoholic degeneration (n = 6) and multiple system atrophy of cerebellar type (n = 2); 3 patients (6.3%) with genetic ataxias were identified using routine DNA tests, such as with SCA type 1, 2 and 17, and 9 (18.8%) patients with Friedreich's disease. The MPS panel enabled molecular diagnosis of ARA in 8 patients (28.6%): ataxia-telangiectasia (n = 2), SANDO syndrome (n = 2), ataxia with oculomotor apraxia type 2 (n = 1), SCAR10 (n = 1), SCAR16 (n = 1), and atypical form of neuroaxonal dystrophy (n = 1). The diagnosis was not established in 20 patients.CONCLUSION:We have proposed an appropriate algorithm for degenerative ataxia diagnosis which is recommended to be used when examining patients with sporadic and autosomal recessive cases of the disorders with dyscoordination of movements.

Болезнь Фридрейха (БФ) — наиболее частая аутосомно-рецессивная атаксия, связанная с экспансией тандемных некодирующих GAA-повторов в гене FXN. Нарушение транскрипции и недостаточность белка фратаксина являются ключевыми звеньями патогенеза заболевания. Целью работы было исследовать экспрессию мРНК гена FXN и провести анализ клинических, генетических и эпигенетических корреляций в группе пациентов с гомозиготной экспансией повторов, в группе их родственников с гетерозиготной экспансией и в контрольной группе. Уровень мРНК гена FXN определяли с помощью полимеразной цепной реакции в реальном времени. Паттерн метилирования CpG-сайтов оценивали методом прямого секвенирования после бисульфитной обработки. В результате работы получены разграничительные значения между группой пациентов БФ, группой гетерозиготных носителей и контрольной группой (15 и 79% соответственно). При проведении клинико-генетических сопоставлений с уровнем экспрессии FXN значимых корреляций выявлено не было. При сопоставлении экспрессии гена c эпигенетическим профилем было установлено, что экспрессия подавляется при гиперметилировании ряда CpG-сайтов выше области тринуклеотидных повторов и некоторых не-CpG-сайтов ниже области повторов. Таким образом, выявленные сайты могут быть рассмотрены в качестве точки приложения таргетного эпигенетического редактирования для увеличения транскрипции FXN и, следовательно, для таргетной терапии заболевания.

Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia associated with the non-coding GAA tandem repeats expansion in the FXN gene. Transcription impairment and frataxin protein deficiency are the key features of the disease pathogenesis. Our research was aimed to study the FXN gene mRNA expression as well as to carry out the clinical, genetic and epigenetic correlation analysis in a group of patients with homozygous expansion, in a group of their relatives with heterozygous expansion and in a control group. The FXN mRNA level was determined using the real-time polymerase chain reaction. Methylation pattern of CpG sites was evaluated by direct bisulfite sequencing. As a result of the study, the threshold values were obtained between the FRDA patients group, the group of heterozygous carriers and the control group (15 and 79%, respectively). The clinical and genetic features comparison with the FXN expression level revealed no significant correlation. When comparing gene expression with an epigenetic profile, it was found that hypermethylation of a number of CpG sites upstream of the trinucleotide repeats and some non-CpG sites downstream of the region of repeats inhibited expression. Thus, the identified methylated sites may be considered as a target for epigenome editing to increase the FXN transcription and, consequently, for target therapy of the disease.

DYT6 is a recently described autosomal dominant form of primarydystonia with early onset of symptoms caused by mutationsin THAP1 gene in chromosome 8. The incidence of this formin various populations is extremely variable and ranges from 1%to 25%. Knowledge of the molecular defect underlying the diseaselargely determines its prognosis and treatment approaches.The article presents the first in the Russian population case ofDYT6 dystonia, which was confirmed by detection of c.424AG (p.T142A) mutation in THAP1 gene. Clinical presentation includedacute manifestation of symptoms at the age of 27 yearswith the development of left-directed latero-retrocollis. The incidenceof this form of dystonia in our population of dystonicsyndromes was 0.7%. We emphasize phenotypic polymorphismof DYT6 dystonia and the role of genetic testing in its diagnosis.

AIM:To evaluate the long-term safety and efficacy of intrajejunal levodopa-carbidopa intestinal gel (LCIG) infusion in the treatment of patients with severe stages of Parkinson disease (PD) who did not respond adequately to treatment with oral drugs.MATERIAL AND METHODS:A large-scale international prospective open-label 54-week study of LCIG in patients with PD with severe motor fluctuations was carried out. A total of 48 patients were enrolled in Russia, 46 patients (95.8%) had PEG-J inserted, and 43 of them completed the study. The safety, including adverse events (AEs), infusion system and pump failures analysis, number of patients completely terminated the study, and efficacy (duration of "off" periods, "on" periods with or without troublesome dyskinesias, UPDRS scores, Clinical Global Impression, Quality of Life (PDQ-39, EQ-5D и EQ-VAS) dynamics, an analysis of patient's diaries) were assessed throughout the whole study.RESULTS:The majority of AEs were mild or moderate with most AEs connected with infusion system application (28.3% patients) including procedure pain. Serious AEs were registered in 8 patients (16.7%). 3 patients (6.3%) discontinued their participation in the study due to AEs. Mean duration of "off" periods by the end of the study decreased by 5.35±2.59 hours (p<0.001), duration of "on" periods without troublesome dyskinesia increased by 5.74±3.91 hours (p<0.001), reduction of "on" periods duration with troublesome dyskinesia became statistically significant by week 36 (p=0.020). The statistically significant improvement of UPDRS (generally and in respect to sub-scales), Clinical Global Impression, and Quality of Life scores was observed throughout the study. Levodopa dose remained stable throughout the 54 treatment weeks. Forty-three patients (93.5%) received LCIG monotherapy throughout the whole study.CONCLUSION:LCIG intrajejunal infusion during 54 weeks showed the favorable safety profile, high tolerability, and efficacy in PD motor symptoms correction.

Neurological syndromes caused by production of antibodies toglutamic acid decarboxylase (GAD65) are a relatively new areaof modern clinical neurology, which is of great theoretical andpractical interest. High titer of identified antibodies is a not alwaysspecific, but highly sensitive, marker for autoimmune CNSdisorders. The authors present their own clinical observationsand an analysis of the literature on a wide phenotypic range ofGAD65-associated pathologies.

Neurological disorders associated with glutamic acid decarboxylase (GAD65) antibodies represent a relatively new field of research in the modern clinical neurology and are of great theoretical and practical interest. High titer of anti-GAD65 antibodies is a highly sensitive, though not always specific, marker of the autoimmune disorders of the central nervous system (CNS). Literature review and authors' clinical observations of the phenotypic heterogeneity of GAD65-associated disorders are presented in the paper.

The carried-out comparative analysis of antibiotic resistance of the microflora allocated from the surface of fauces and deep parts of lacunas of palatine tonsils in 102 patients with decompensation of the CT showed the absence of β-hemolytic streptococcus of group A (Str.pyogenes) in the microflora, prevalence of resistant strains of St.aureus and its mixed-options, higher resistance of the microorganisms allocated from the depth of tonsils to antibiotics.

DYT6 is a recently described autosomal dominant form of primary dystonia with early onset of symptoms caused by mutations in THAP1 gene in chromosome 8. The incidence of this form in various populations is extremely variable and ranges from 1% to 25%. Knowledge of the molecular defect underlying the disease largely determines its prognosis and treatment approaches. The article presents the first in the Russian population case of DYT6 dystonia, which was confirmed by detection of c.424A> G (p.T142A) mutation in THAP1 gene. Clinical presentation included acute manifestation of symptoms at the age of 27 years with the development of leftdirected lateroretrocollis. The incidence of this form of dystonia in our population of dystonic syndromes was 0.7%. We emphasize phenotypic polymorphism of DYT6 dystonia and the role of genetic testing in its diagnosis.

The objective of the research is to study neonatal adaptation in new-born children from the tobacco abused mothers. A comparative analysis of clinical and neuroendochnal status and lipid metabolism in new-born children from smoking and non-smoking mothers was carried out Neonatal adaptation disorders were revealed in new-born children from the smoking mothers.

The results of treatment with noben (idebenon), an improved structural analogue of coenzyme Q10, of 34 patients with Friedrich's disease are presented. In all cases, the clinical diagnosis was confirmed by the presence of a typical mutation, an expansion of trinucleotide GAA-repeats, in the FRDA gene. All patients received noben as a main drug in dosage 5 mg/kg daily during 3 months. An examination of the patients included modern laboratory and instrumental methods, analysis of levels of lactic and pyruvic acids and their ratio in the peripheral blood. Also parameters of lipid peroxidation and mitochondrial dehydrogenase activity in peripheral lymphocytes were studied. Positive changes were found in the majority of patients for muscle strength in extremities, tolerability to physical loadings, general fatigue, movement activity, speech and coordination functions, along with significant improvement of biochemical and cytochemical status. The results obtained suggest a positive effect of noben on cell energy metabolism in this severe disorder from the group of mitochondrial cytopathies.