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The potentialities in the application of the discourse analysis method to study a political discourse as a current political practice are shown. The authors, using the Foucault methodology, offer a sociological definition for the political discourse. It is the authors’ opinion that the approach mentioned allows investigating a political discourse as a practice for the formation of a certain reality, specific agents, institutions and organizations. A political discourse is a simulative dynamic model of political area where various subdiscourses interact, thus creating their own ideas of policy, symbols and images. Subdiscourses of political leaders become dominating. Inasmuch as a political discourse in a current political system is carried out with the aid of mass media, it could be considered as a media discourse of policy. The authors consider the representation as a basic mechanism for the formation of a political discourse, by the example of the representation of the image of V.V. Putin, the President of the Russian Federation. The representation of a political leader image in a political discourse has a number of peculiarities. It is carried out on the basis of certain principles with the aid of the system of political codes. Empiric investigations allowed making a conclusion that the main symbolic image for the Russian President is an image of a super-hero. It is the authors’ opinion, the image of V.V. Putin as a leader super-hero is determined by the specificity of the Russian political culture within the limits of which a leader is a center of power establishing an authoritarian style of ruling. The authors show the process of the political legitimacy displacement from the institutional level to the personal one by means of mass media. A political leader gains a status of a subject establishing moral, social and value reference points for the whole of the society.

Zhu–Tokita–Takenouchi–Kim syndrome (ZTTK syndrome) is a rare autosomal dominant nuclear speckleopathy characterized by developmental delay, hypotonia, intellectual disability, facial dysmorphism in association with variable brain malformations, musculoskeletal abnormalities and ocular involvement. Currently, 87 cases of ZTTK syndrome have been described worldwide. The syndrome caused by mutations in the SON gene, located on the long arm of chromosome 21 (21q22.11). Nonsense and frameshift mutations have been described in the SON gene. Missense mutations, partial or whole gene deletions are less common.The aim of the work is to analyze the clinical picture and molecular genetic results of patients with confirmed ZTTK syndrome and compare them with data from foreign literature.We observed the one boy and two girls with ZTTK syndrome aged 13 months to 59 months, averaging about 38 months. DNA diagnostic was performed by next generation sequencing. All patients and all parents were confirmed by Sanger sequening. Three pathogenic variants were identified: c.5753_5756delTTAG (p.Val1918Glufs*87), c.1531del (p.Thr511Glnfs*9) and c.403delG (p.Glu135Asnfs*14). The first one was is most common, the other two are novel variants. Most patients had growth, motor and speech delay, seizures, hypotonia, congenital heart defects, urinary tract abnormalities and brain malformations. Comparative analysis of facial features in patients with ZTTK syndrome showed downslanting palpebral fissures, epicantal folds, broad or depressed nasal bridge, flared nares, smooth philtrum, thin upper lip and low set, rotated ears. The use of next generation sequencing as a first‑line test for research and diagnostic of ZTTK syndrome is advisable due to the pronounced clinical polymorphism.

Incontinentia pigmenti, also known as Bloch–Sulzberger syndrome, is a rare hereditary disease characterized by typical skin rashes and involvement of other organs and systems. Magnetic resonance imaging stands as the primary method for visualizing the structural pathology of the brain and predicting neurological manifestations in an affected child. Diagnosing incontinentia pigmenti predominantly falls within the domain of dermatologists; verification is performed by molecular genetic analysis of the IKBKG gene. This study involved magnetic resonance imaging of the brain in a patient with skin rashes, characteristic of Bloch–Sulzberger syndrome, and deletion in the IKBKG gene, where numerous foci of ischemia, hemorrhages, and lesions of the tracts were detected. Magnetic resonance imaging of the brain in patients with Bloch–Sulzberger syndrome is used to evaluate the severity of damage to the brain substance, which makes it possible to explain the cause of neurological symptoms and correct habilitation, as well as predict the development of the child.

IntroductionThe blockade of interleukine-1 (anakinra and canakinumab) is a well-known highly effective tool for monogenic autoinflammatory diseases (AIDs), such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, hyperimmunoglobulinaemia D syndrome, and cryopyrin-associated periodic syndrome, but this treatment has not been assessed for patients with undifferentiated AIDs (uAIDs). Our study aimed to assess the safety and efficacy of canakinumab for patients with uAIDs.MethodsInformation on 32 patients with uAIDs was retrospectively collected and analyzed. Next-generation sequencing and Federici criteria were used for the exclusion of the known monogenic AID.ResultsThe median age of the first episode was 2.5 years (IQR: 1.3; 5.5), that of the disease diagnosis was 5.7 years (IQR: 2.5;12.7), and that of diagnostic delay was 1.1 years (IQR: 0.4; 6.1). Patients had variations in the following genes: IL10, NLRP12, STAT2, C8B, LPIN2, NLRC4, PSMB8, PRF1, CARD14, IFIH1, LYST, NFAT5, PLCG2, COPA, IL23R, STXBP2, IL36RN, JAK1, DDX58, LACC1, LRBA, TNFRSF11A, PTHR1, STAT4, TNFRSF1B, TNFAIP3, TREX1, and SLC7A7. The main clinical features were fever (100%), rash (91%; maculopapular predominantly), joint involvement (72%), splenomegaly (66%), hepatomegaly (59%), lymphadenopathy (50%), myalgia (28%), heart involvement (31%), intestinal involvement (19%); eye involvement (9%), pleuritis (16%), ascites (6%), deafness, hydrocephalia (3%), and failure to thrive (25%). Initial treatment before canakinumab consisted of non-biologic therapies: non-steroidal anti-inflammatory drugs (NSAID) (91%), corticosteroids (88%), methotrexate (38%), intravenous immunoglobulin (IVIG) (34%), cyclosporine A (25%), colchicine (6%) cyclophosphamide (6%), sulfasalazine (3%), mycophenolate mofetil (3%), hydroxychloroquine (3%), and biologic drugs: tocilizumab (62%), sarilumab, etanercept, adalimumab, rituximab, and infliximab (all 3%). Canakinumab induced complete remission in 27 patients (84%) and partial remission in one patient (3%). Two patients (6%) were primary non-responders, and two patients (6%) further developed secondary inefficacy. All patients with partial efficacy or inefficacy were switched to tocilizumab (n = 4) and sarilumab (n = 1). The total duration of canakinumab treatment was 3.6 (0.1; 8.7) years. During the study, there were no reported Serious Adverse Events (SAEs). The patients experienced non-frequent mild respiratory infections at a rate that is similar as before canakinumab is administered. Additionally, one patient developed leucopenia, but it was not necessary to stop canakinumab for this patient.ConclusionThe treatment of patients with uAIDs using canakinumab was safe and effective. Further randomized clinical trials are required to confirm the efficacy and safety.

Aromatic L‑amino acid decarboxylase (AADC) deficiency is rare autosomal recessive neurometabolic disorder. It caused by generalized combined deficiency of serotonin, dopamine, norepinephrine and adrenaline. This disorder is characterized by muscular hypotonia, motor development delay, oculogyric crises and impairment of the autonomic nervous system.Laboratory diagnostic of AADC deficiency in Russian Federation includes determination of the concentration of 3‑O‑methyldophamine in dried blood spots by tandem mass spectrometry and molecular analysis of the DDC gene by Sanger sequencing or next generation sequencing.Therapy of AADC deficiency includes combination of drugs which increase the formation of dopamine, inhibit its reuptake and increase the residual activity of the enzyme. The first‑line drugs are selective dopamine agonists, monoamine oxidase inhibitors of type B and vitamin B6 supplements.We present the case of management and treatment of patients with AADC deficiency. The patient’s condition was improved by using of combination therapy with pyridoxal‑5‑phosphate, pramipexole and selegiline. Significant positive dynamics was achieved on pyridoxal‑5‑phosphate therapy for the first time.

Abstract Background There is a vast number of screening studies described in the literature from the beginning of the twenty-first century to the present day. Many of these studies are related to the estimation of Fabry disease (FD) morbidity among patients from high-risk groups, including adult patients with hypertrophic cardiomyopathy (HCM) and left ventricular hypertrophy (LVH). These studies show diverse detection frequencies (0–12%) depending on the methodology. Our study is the only example of large-scale selective FD screening based on the implementation of next-generation sequencing technology (NGS) as a first-level test to estimate FD morbidity in the Russian population over 18 years of age burdened with HCM. Methods The study included 1009 patients (578 males and 431 females), with a median age of 50 years, who were diagnosed with HCM according to current clinical guidelines. In the first stage of screening, all patients underwent molecular genetic testing (NGS method) of target regions. These regions included the coding sequences of 17 genes and mutations that can lead to the development of HCM. Lysosomal globotriaosylsphingosine (lyso-Gb3) concentrations and α-galactosidase A (α-gal A) enzyme activity were measured in the second stage of screening to reveal pathogenic or likely pathogenic variants in the GLA gene. Results We revealed 8 (0.8%) patients (3 (37.5%) males and 5 (62.5%) females) with an average age of 59 ± 13.3 years who had pathogenic, likely pathogenic variants and variants of uncertain significance (VUS) in the GLA gene (NM_000169.2) as a result of selective screening of 1009 Russian patients with HCM. FD was confirmed via biochemical tests in a male with the pathogenic variant c.902G > A, p.R301Q as well as in two females with likely pathogenic variants c.897C > A, p.D299E and c.1287_1288dup, p.*430Fext*?. These tests showed reduced enzymatic activity and increased substrate concentration. However, a female with the pathogenic variant c.416A > G, p.N139S and with normal enzymatic activity only had increased substrate concentrations. The revealed nucleotide variants and high values of biochemical indicators (lyso-Gb3) in these 4 patients allowed us to estimate the FD diagnosis among 1009 Russian patients with HCM. Mild extracardiac manifestations were observed in these four patients; however, both biochemical values within the reference range in females with the c.971T > G, p.L324W (VUS) variant. α-gal A activity and lyso-Gb3 concentrations were also within the normal range in two males with hemizygous variants, c.546T > C, p.D182D and c.640-794_640-791del (we regarded them as VUS), and in one female with the c.427G > A, p.A143T variant (with conflicting interpretations of pathogenicity). Conclusion The prevalence rate of FD among 1,009 adult Russian patients with HCM was 0.4%. We recommend FD screening among adult patients of both sexes with HCM and an undefined genetic cause via NGS method with subsequent analysis of α-gal A activity and lyso-Gb3 concentration in patients with pathogenic, likely pathogenic variants, and VUS. This strategy identifies patients with an atypical form of FD that is characterized by high residual activity of α-gal A, low concentrations of lyso-Gb3, and minor extracardiac manifestations.

Background. Nowadays, dermatoses with mixed clinical picture and resistant to classical management become more common. The presence of various genetic disorders typical for most chronic dermatoses may indicate possible combination of several nosologies.Clinical Case Description. The article presents the clinical case of multimorbid condition in 10 years old patient who has nucleotide variants in CARD14 and EXPH5 genes. Mutations in CARD14 gene are typical for patients with type 2 psoriasis and pityriasis rubra pilaris (autosomal dominant type), while mutations in EXPH5 gene are typical for patients with non-specific epidermolysis bullosa (autosomal recessive type). Mutation in the TGM1 gene that is described in patients with congenital ichthyosis (autosomal recessive type), pathogenic mutations in KRT74 gene typical for ectodermal dysplasia, hypotrichosis and uncombable hair syndrome, and mutations in the KRT86 gene typical for monilethrix were also revealed. Medical history taking and histological examination as well as clinical data evaluating are crucial for correct diagnosis. They allow to understand the absence of the such manifestations in relatives and reveal various pathological processes in the epidermis. Molecular genetic testing with new generation sequencing (NGS) helps to finally establish the diagnosis and determine the further tactics for patient management.Conclusion. Multidisciplinary approach and use of high-technology methods of examination and treatment (such as molecular genetic testing and biological therapy) are required for final diagnosis in severe forms of chronic dermatosis resistant to treatment and for decision on correct tactics for the further management of such patients.

The article solves the problem of choosing a technology for heat treatment of gears of large diameter based on a system-resource approach for a particular enterprise. To solve the problem, a functional model was developed, the production resources available to the enterprise were analyzed, and the possibilities of developing solutions using system forecasting models were analyzed. Sketches of the solution were developed for transfer to the departments of mechanization and automation for further design and technological development and manufacturing.

Aim. To identify the proportion of restrictive cardiomyopathy (RCM), as well as cardiomyopathy (CMP) with a restrictive type of hemodynamics among all cases of genetic CMP and to determine the relative frequencies and spectrum of nucleotide variants in Russian children with RCM, as well as to search for phenogenotypic correlations.Material and methods. The study included 689 children with CMPs. All children underwent a molecular genetic testing of the target regions of 419 genes responsible for various cardiomyopathies and channelopathies using the method of massively parallel sequencing (MPS).Results. In 668 (97,0%) children, pathogenic, likely pathogenic nucleotide variants, as well as nucleotide variants with unknown clinical significance, were identified. Of these, 45 (6,7%) patients were selected to determine the molecular genetic characteristics of RCM, 20 of whom had clinical symptoms and morphofunctional structure of RCMP (3,0%), while the remaining 25 (3,7%) children were diagnosed with another CMP type with a restrictive type of hemodynamics. In total, these patients had 41 nucleotide variants in 15 different genes, while 19 (46,3%) variants were pathogenic, 12 (29,3%) — likely pathogenic, 10 (24,4%) — uncertain clinical significance. Pathogenic and likely pathogenic variants were identified in a total of 38 (84,4%) patients, while in 19 (42,2%) patients, the pathogenic variants described earlier were found. The most common genetic marker of RCM in Russian children was TNNI3 gene mutations. In total, they were identified in 12 (25%) children: with RCP — 8 (40%) patients; with CMP with a restrictive type of hemodynamics — 4 (16%) patients. At the same time, the most common mutation of the TNNI3 gene was the nucleotide variant c.575G>A, leading to the amino acid variant p.R192H, described earlier in patients with RCM and identified by us in three (15%) unrelated children with RCM. In addition, a significant difference was found between the averaged values of N-terminal pro-brain natriuretic peptide in patients with mutations in the MYH7 and TNNI3 genes (0,0039, p

Simple Summary: Immunotherapy may be beneficial for pancreatic cancer (PC) patients with mismatch repair (MMR) deficiency. Although it is known that MMR deficiency (MMR-D) can result from mutations in MMR genes, the prevalence of these mutations and their impact on the formation of the MMR-D phenotype in PC have been insufficiently researched. Microsatellite instability (MSI) is a hallmark of MMR-D. Here, we estimated the frequency of germline and somatic mutations in the three MMR genes (MLH1, MSH2, and MSH6) in PC patients, estimated the prevalence of MSI, and assessed the relationship between MMR genes mutations and MSI status in PC. In our study of an unselected cohort of PC patients, we identified germline and somatic alterations in MMR genes, however these alterations did not contribute to the MMR-D phenotype. Our findings underscore the necessity of evaluating tumor MMR-D status in PC patients with confirmed Lynch syndrome when deciding whether to administer immunotherapy. Patients with pancreatic cancer (PC) showing mismatch repair (MMR) deficiency may benefit from immunotherapy. Microsatellite instability (MSI) is a hallmark of MMR deficiency (MMR-D). Here, we estimated the prevalence of MSI in PC, investigated germline and somatic mutations in the three MMR genes (MLH1, MSH2, and MSH6), and assessed the relationship between MMR genes mutations and MSI status in PC. Clinical specimens from PC patients were analyzed using targeted next-generation sequencing, including paired normal and tumor specimens from 155 patients, tumor-only specimens from 86 patients, and normal-only specimens from 379 patients. The MSI status of 235 PCs was assessed via PCR. Pathogenic/likely pathogenic (P/LP) germline variants in the MMR genes were identified in 1.1% of patients, while somatic variants were found in 2.6% of patients. No MSI-H tumors were detected. One patient carried two variants (P (VAF = 0.57) and LP (VAF = 0.25)) simultaneously; however, their germline/somatic status remains unknown due to the investigation focusing solely on the tumor and MSI analysis was not performed for this patient. MSI is rare in PC, even in tumors with MMR genes mutations. Our findings underscore the importance of assessing tumor MMR-D status in PC patients with confirmed Lynch syndrome when deciding whether to prescribe immunotherapy. [ABSTRACT FROM AUTHOR]

Background. Cryopyrin-associated periodic syndromes is a group of rare congenital autoinflammatory diseases such as familial cold autoinflammatory syndrome, Muckle-Wells syndrome and chronic infantile neurological cutaneous articular syndrome. These syndromes are considered as clinical variants of one disease with different intensity of clinical features and severity of pathologic process. The onset of these syndromes is usually on the first year of life, and they start with fever, urticarial rash, various variants of joint diseases (from arthralgia to residual and persistent arthritis) and nervous system disturbances. There are only single case reports of cryopyrin-associated periodic syndromes in Russia.Clinical Case Description. The disease onset was at the age of 1 year 8 months with fever and rash as well as generalized joint syndrome. Autoinflammatory syndrome was suspected due to to results of blood tests, MRI, molecular genetic testing. Exons 2, 3 and 4 of TNFRSF1A gene and exon 4 of NLRP3 gene with nearby introns were studied with the method of direct automated sequencing. The c.943A>G variant in heterozygous state in NLRP3 gene was revealed. The child was treated with IL-1 beta inhibitor (canakinumab) with positive effect.Conclusion. Diagnostics of cryopyrin-associated periodic syndrome in children is the serious challenge. Timely decision with help of molecular genetic methods is crucial for successful target therapy.

Abstract Laboratory diagnostics of lysosomal acid lipase deficiency (LAL‐D), a rare disorder associated with LIPA alterations, are based on the evaluation of LAL activity. In dry blood spots (DBS) submitted for LAL‐D diagnostics (the screening cohort) over a two‐year period or obtained from a cohort of retrospective LAL‐D patients, we measured: (1) LAL activity using a two‐reaction assay with 4‐methylumbelliferone palmitate (4‐MU‐Palm) and Lalistat‐2, a specific LAL inactivator; (2) total lipase (TL) activity by a 1‐hour kinetic 4‐MU‐Palm cleavage reaction (no Lalistat‐2). The TL activity was expressed as the area under the kinetic curve after 1 hour (TL‐AUC1h) of the reaction and presented as the median (min‐max). LAL activity was reduced in 30/537 individuals from the screening cohort, among which LIPA sequencing revealed six patients and one carrier. Overall, 16 (89%) individuals among six novel and 12 retrospective LAL‐D patients carried at least one c.894G>A mutation (six were homozygous). The TL‐AUC1h in nonLAL‐D specimens with normal LAL activity (n = 90) was unambiguously higher (9471 [4015‐23 585] RFU*h/punch) compared to LAL‐D patients, including six new and nine retrospective patients (1810 [357‐2608] RFU*h/punch). Importantly, in 13/15 examined nonLAL‐D specimens with reduced LAL activity the TL‐AUC1h was above a threshold of 2652 RFU*h/punch. Applying this threshold, the TL‐AUC1h index discriminated all LAL‐D patients (100% sensitivity) and 103/105 nonLAL‐D specimens (98% specificity). Given that there is no need for Lalistat‐2 and two parallel enzymatic reactions in conjunction with high sensitivity and specificity, the kinetic assay seems to be practical for LAL‐D screening. Synopsis Lysosomal acid lipase deficiency responsible for Wolman disease and cholesterol ester storage disease could be reliably detected using a kinetic assay of total lipase activity with a fluorogenic substrate.

Osteogenesis imperfect is genetically heterogeneous group of diseases which are characterized by bone brittleness and fractures. It was thought for a long time that this is happening due to mutations in collagen genes. However, within past decade the understanding of osteogenesis imperfecta etiology has changed as a result of genetics development. The majority of all cases is related to mutations in collagen genes whereas rare mostly recessive forms are related to mutations in genes encoding collagen post-translational modification. Mutations in SERPINF1 gene were chosen as molecular cause of osteogenesis imperfecta type VI in 2011. Thus the new pathophysiology of this disease was revealed. Children with osteogenesis imperfecta type VI have high-frequency of fractures despite the management with bisphosphonates because mineralized bone osteoid is considerably reduced.

The expression “rightly proclaim the word of Thy truth” from the formula of the Eucharistic ascension of the Bishop’s name is one of the most difficult to understand and difficult to translate in Orthodox worship. The paper studies the history of the verb ὀρθοτομέω using and its equivalents in religious dictionaries of different peoples, shedding light on the true meaning of the formula under consideration. The author of the paper finds parallels between the verb ὀρθοτομέω and the “cutting of the Covenant” in the religions and cults of Near Asia, particularly in the Biblical religion, and also concludes the “priestly” interpretation of the Bishop’s ministry in the Second Epistle of St. Paul to Timothy.

Osteogenesis imperfect (OI) is a rare genetic disease of connective tissue, the main manifestation are fractures that are developing due to increased bone fragility in both children and adults. Currently, it is known that the genetic basis of the disease in 90% of cases are violations in the genes COL1A1 and COL1A2. Diagnosis of this disease is mostly based on clinical and radiological data; some laboratory parameters of blood and urine can provide additional information but, due to the low specificity, these tests are not widely used in clinical practice when diagnosing the bone pathology. Separate extensive problem is the realization of timely differential diagnosis followed by the establishment of correct diagnosis and development of the right tactics. Currently, the standard of management of patients with OI is a multidisciplinary approach that allows to perform the necessary examination of a child, to make an accurate diagnosis, and start the therapy in time. A practitioneer should have sufficient knowledge about the disease and be able to apply it practically to realize the treatment tactics.

Background. Non-compaction cardiomyopathy is a group of genetically heterogeneous, poorly studied myocardial diseases with a variety of clinical manifestations (from asymptomatic course to progressive systolic dysfunction with symptoms of chronic heart failure, arrhythmias, and thromboembolic complications). Considering the variety of genetic disorders associated with the development of noncompaction cardiomyopathy, genetic verification of the diagnosis is important for determining the prognosis and conducting genetic counselling of families with cases of the disease.Description of the Clinical Case. The article presents two clinical observations of a severe course of non-compaction cardiomyopathy with remodeling of the heart cavities according to the dilated phenotype. In order to clarify the disease etiology, a molecular genetic study was conducted using the method of direct automatic sequencing with the analysis of targeted regions of 404 genes which mutations are described in hereditary diseases of the heart and blood vessels. After verifying the mutation (in the ACTC1 and MYBPC3 genes), we performed a search for the detected nucleotide substitution in the venous blood samples of parents and in one case — in the fetal DNA sample. The mode of inheritance has been determined; the probability of recurrence of the disease in siblings in subsequent pregnancies has been estimated.Conclusion. The description of clinical cases shows the importance of genetic verification of the diagnosis in patients with non-compaction cardiomyopathy for determining the disease prognosis and developing an algorithm for monitoring relatives of a proband.

Mitochondrial respiratory chain complex V deficiency, type 2 is a rare hereditary disease developing due to mutations in TMEM70 (transmembrane protein 70) gene. Using massively parallel sequencing in patient with phenotype features, noncompaction of the left ventricular myocardium, and congenital heart disorder, we revealed mutations c.317-2A>G and c.578_579del in TMEM70 gene both in a heterozygous state. The mutations were confirmed by bi-directional automatic sequencing.

Background. Cystic fibrosis is a hereditary disease that occurs as a result of mutations in the regulator gene of chloride ion transmembrane transport (CFTR). Finding mutations in the CFTR gene is necessary for identification of the clinical features of cystic fibrosis.Objective. Our aim was to identify genotype-phenotype correlations between mutations of the first class of pathogenicity and clinical manifestations of cystic fibrosis based on studying the prevalence and structure of CFTR gene mutations.Methods. The study included children under 18 years with cystic fibrosis admitted to hospital between 2013 and 2017. Biallelic mutations in the CFTR gene were the noninclusion criterion. The CFTR gene variants were analyzed by next-generation sequencing method.Results. In 125 patients with cystic fibrosis, 59 different variants of the CFTR gene were detected, 11 of them not previously described. The most common was the deletion c.1521_1523del found in 98 (39.2%) of the 250 analyzed CFTR gene alleles and the deletion c.1545_1546del found in 22/250 (8.8%) alleles. It has been shown that the mutation c.1545_1546del, p.Y515* was more often found in children of the Chechen nation — odds ratio (OR) 139 (95% confidence interval 15–1,257). It has been established that meconium ileus, pancreatic deficiency and cirrhosis are more common in patients with mutations of the first category of pathogenicity: OR 3.9 (95% CI 1.0–15.0), 4.4 (95% CI 1.8–11.1), and 351 (95% CI 17.5–7,046), respectively. The association of CFTR gene mutations with the development of bronchiectases and polypous pancinusitis has not been found.Conclusion. Correlations between the genotype and clinical manifestations of cystic fibrosis in Russian children with CFTR gene mutations of the first class of pathogenicity have been established.

Homocystinuria is a genetically heterogeneous hereditary disease from the group of aminoacidopathies caused by a metabolic disorder of sulphur-containing amino acids, primarily methionine. The article presents the etiopathogenetic, diagnostic and therapeutic aspects of this disease and covers modern opportunities of biochemical and molecular diagnostics. The approach to dietary and pharmacological correction of metabolic disorders in homocystinuria and the general strategy of patients’ management are described in detail. Important information is given for physicians of various disciplines and parents of patients.