Updating preventive measures of children disability

The article provides an overview of special literature, which gives an opportunity to redefine some issues of disability prevention in children with rare (orphan) diseases, which will improve the organizational measures in this area. The prevention of children’s disability is considered as a system of measures to protect the health of the mother and child throughout childhood. The early disability prevention system in children and support for families raising children with disabilities remain among the main priorities of the State social policy of the Russian Federation. The authors describe modern technologies for reducing the genetic burden in the population from the point of view of preventing hereditary and congenital pathologies. They identify the priority areas of disability prevention in children with rare (orphan) diseases, i.e. introduction of prenatal and preimplantation diagnostics; use of the Prenatal Consultation organizational model; conducting a wider screening for congenital and hereditary metabolic diseases with the inclusion of the most common nosological forms of rare (orphan) diseases; finding pathogenetic therapy methods; increasing the knowledge of pediatricians about rare (orphan) diseases.

Inherited metabolic diseases: aminoacidopathies, organic acidemia, defects of mitochondrial β-oxidation. A brief overview

Inherited metabolic diseases are a large group of inherited monogenic diseases. Metabolic disorders can cause child disability and mortality. Tandem mass spectrometry is a powerful technology that allows to diagnosis a large number of hereditary metabolic diseases. Clinical manifestations are variable, but more often the damages of nervous system, heart, liver, kidneys, hyperammonemia, hypo/hyperglycemia take place. The disease can make its debut at any age, but the severe forms of the disease manifest at infancy. Early diagnosis and treatment can significantly improve the prognosis; many countries expand the list of diseases included in screening programs. At the beginning of 2021 in most regions of the Russian Federation mass newborn screening is carried out for five hereditary metabolic diseases. The age and the range of clinical manifestation are variable; therefore, knowledge of this pathology is very important both for pediatricians and therapists, and for specialized doctors. The article presents a brief description of next groups of metabolic diseases: aminoacidopathies, organic acidurias and fatty acid oxidation defects.

MODELS AND METHODS OF INFORMATION TECHNOLOGY OF ADVANCED NEONOTAL SCREENING

The paper considers the problems of informational implementation of neonatal screening of newborns in order to improve the overall picture of the nation's health and prevent the development of hereditary diseases. The methodology for solving the problems of complete neonatal screening is based on the methods and mathematical apparatus of discrete mathematics, web technologies, data warehouses, and data mining methods. An information model of the dynamic processes of neonatal screening is proposed, based on the specific processing of data presented by a tuple, which contains coherent sequential processes for obtaining the results of tests for blood analysis of newborns, conducting genetic studies and determining pathologies and deviations from an expanded list (currently up to 44 indicators for the purpose of exiting for more than 60). The block diagram of information support of information technology in the decision support system for carrying out neonatal screening of hereditary metabolic diseases is presented. On the basis of LLC «CDC «PHARMBIOTEST», the research of the algorithm for performing sequential procedures of neonatal screening was carried out. The described algorithm of actions has been tested and fully tested for the continuity of information flows, the stability of the information model graph. As a result of the research, the sufficiency and completeness of the chronological indicators of the processing of information flows have been proved. The criteria for confirming the authenticity of methods for obtaining a diagnosis have been developed.

Differential diagnosis of hereditary metabolic diseases using the expert knowledge-based system

Aim. The aim of the study was to create a computer decision support system using expert knowledge for the diagnosis of rare hereditary diseases due to the difficulty of their identification at the pre-laboratory stage.Material and Methods. Descriptions of the clinical picture of lysosomal storage diseases from literature sources were used as the research material. The methods included knowledge extraction, expert assessments, quantization of age intervals, and applied intelligent services to form a knowledge base.Results. The results of the study include the construction of models for a complex assessment of a sign and an integral assessment of a disease, on the basis of which the comparative analysis algorithm is implemented to assess each of the hypotheses put forward by the system. The results of testing the prototype of the created expert system on a control sample of patients with mucopolysaccharidosis showed the efficiency of 90%. Discussion. In the discussion, several diagnostic systems are considered and their distinction from the system, presented in this work, is shown.Conclusion. The results of the development of intelligent system based on knowledge for the diagnosis of lysosomal storage diseases are summarized and the perspectives for its development are highlighted.

The impact of COVID-19 on rare metabolic patients and healthcare providers: results from two MetabERN surveys

The ongoing coronavirus disease 2019 (COVID-19) pandemic has caused disruption in all aspects of daily life, including the management and treatment of rare inherited metabolic disorders (IMDs). To perform a preliminary assessment of the incidence of COVID-19 in IMD patients and the impact of the coronavirus emergency on the rare metabolic community between March and April 2020, the European Reference Network for Hereditary Metabolic Diseases (MetabERN) has performed two surveys: one directed to patients’ organizations (PO) and one directed to healthcare providers (HCPs). The COVID-19 incidence in the population of rare metabolic patients was lower than that of the general European population (72.9 × 100,000 vs. 117 × 100,000). However, patients experienced extensive disruption of care, with the majority of appointments and treatments cancelled, reduced, or postponed. Almost all HCPs (90%) were able to substitute face-to-face visits with telemedicine, about half of patients facing treatment changes switched from hospital to home therapy, and a quarter reported difficulties in getting their medicines. During the first weeks of emergency, when patients and families lacked relevant information, most HCPs contacted their patients to provide them with support and information. Since IMD patients require constant follow-up and treatment adjustments to control their disease and avoid degradation of their condition, the results of our surveys are relevant for national health systems in order to ensure appropriate care for IMD patients. They highlight strong links in an interconnected community of HCPs and PO, who are able to work quickly and effectively together to support and protect fragile persons during crisis. However, additional studies are needed to better appreciate the actual impact of COVID-19 on IMD patients’ health and the mid- and long-term effects of the pandemic on their wellbeing.

Clinical and Laboratory Markers of Hereditary Metabolic Diseases in Children of the First Half of Life

A significant contribution to the morbidity and mortality of children is due to hereditary pathology, which is manifested by high mortality. Aim of the research. To study the frequency of occurrence, structure and clinical and laboratory markers of hereditary metabolic diseases in children of the first half of the year with suspicion of this pathology. Materials and methods. A retrospective analysis of case histories (form No. 003/y) and a face-to-face examination of patients directed to blood tests by tandem mass spectrometry, from Surgery Unit No. 2 for Newborns and Premature Babies and from the Unit of Pathology of Newborns, (Ivano-Matryoninskaya City Children’s Clinical Hospital, Irkutsk). Results. In 2019, 21 children with suspected hereditary metabolic diseases were examined using the tandem mass spectrometry method in the above mentioned departments. All of them had at least one of the main clinical criteria for hereditary metabolic diseases: 67 % had hepatomegaly in combination with an increase in the level of liver enzymes, 43 % had a hereditary history and metabolic acidosis, 33 % showed a sudden deterioration after a period of normal development, 24 % had hypoglycemia, and 14 % had an abnormal urine or body odor, in 4.7 % of cases there was an increase in ketone bodies in the blood and (or) urine. All children identified from 3 to 7 additional criteria, which are indications for examination on the hereditary metabolic diseases. The results of the study revealed 5 children with hereditary metabolic diseases namely amino acid metabolism. 90 % of them had a burdened hereditary history, 100 % had a concomitant pathology – hepatitis and cholestatic lesions of the liver, anemia, an open oval window and others. Conclusion. Despite the obvious economic and medical significance of preclinical identification of patients with hereditary metabolic diseases, the screening problem contains many open questions that need to be addressed at all levels of the organization.

Results of neonatal screening for hereditary metabolic diseases in the Republic of Kazakhstan for 2019 year

Массовое обследование новорождённых в программе неонатального скрининга в Республике Казахстан проводится на 2 наследственных заболевания - фенилкетонурию и врожденный гипотиреоз. В 2019 году был проведен пилотный проект исследований методом тандемной масс-спектрометрии 1000 детей до 1 года на 49 наследственных болезней обмена. Mass examination of newborns in the neonatal screening program in the Republic of Kazakhstan is carried out for 2 hereditary diseases - phenylketonuria and congenital hypothyroidism. In 2019 pilot project was conducted for 1000 studies using tandem mass spectrometry of children under age of 1 year for 49 hereditary metabolic diseases.

Comparative clinical characterization of the new recessive mucopolysaccharidosis-plus disease in the Yakut and Turkish populations

МПС - группа наследственных болезней обмена веществ, связанных с нарушением метаболизма гликозаминогликанов (ГАГ), приводящая к мультисистемному поражению органов и тканей. Обусловлены данные заболевания мутациями генов, контролирующих процесс внутрилизосомного гидролиза макромолекул. Недавно выявлено новое наследственное заболевание с аутосомно-рецессивным типом наследования, относящееся к группе лизосомных заболеваний, клинически схожее с МПС, с мутацией в гене VPS33A, названное мукополисахаридоз-плюс (МПС-ПС) (OMIM #617303). Оно встречается у детей якутской национальности и приводит к ранней младенческой смертности. Также оно описано одновременно у 2 сибсов из Турции. Описанная впервые мутация c.1492C>T (p.Arg498Trp) в гене VPS33A является причиной МПС-плюс в обеих популяциях. MPS is a group of hereditary metabolic diseases associated with impaired glycosaminoglycan (GAG) metabolism, leading to multisystem damage of organs and tissues. Recently, a group of scientists revealed a new hereditary disease with an autosomal recessive inheritance type, belonging to the lysosomal disease group, clinically similar to MPS, with a mutation in the VPS33A gene, called mucopolysaccharidosis plus (MPS-PS) (OMIM # 617303), found in Yakut children, leading to early infant mortality, and also described simultaneously in 2 siblings from Turkey. The newly described c.1492C> T (p.Arg498Trp) mutation in the VPS33A gene is the cause of MPS-plus in both populations.

Modern neurogenetic representations of MELAS syndrome. Clinical cases (the lecture)

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.