2Tashkent Medical Academy Integration of Science, Education and Practice in Modern Psychology and Pedagogy: Problems and Solutions
Volume 4 | TMA Conference | 2023 Zamonaviy psixologiya, pedagogikada fan, ta'lim va amaliyot integratsiyasi: muammo va yechimlar
CAUSES OF HEREDITARY DISEASES IN CHILDREN AND THEIR
ELIMINATION
Stanislaw Potoczek
Wroclaw Medical University, Poland The Department of Pediatric autonomy in healthcare ru-m@umed.wroc.pl
The article reflects modern data on the prevalence, clinic, diagnosis, including prenatal and neonatal, more common hereditary diseases, the timing of studies for prenatal diagnostics and interpretation of the obtained data. Data on the principles are also presented on therapy of hereditary diseases.
Keywords: children, hereditary diseases, diagnostics, neonatal screening.
Hereditary diseases - diseases, occurrence and the development of which is associated with changes (mutations) in the genetic material. Depending on the nature of the mutations distinguish monogenic hereditary, chromosomal, mitochondrial and multifactorial diseases (E.K. Ginter, 2003). From hereditary diseases should be distinguished congenital diseases that are caused by intrauterinedamage caused, for example, by infection (syphilis or toxoplasmosis) or exposure to other damaging factors on the fetus during pregnancy. According to WHO, 5-7% of newborns have different hereditary pathology, in which monogenic forms account for 3-5%. Number of registered hereditary diseases (ND) is constantly growing [1, 2, 3, 8]. Many genetically determined diseases do not appear immediately after birth, and after some, sometimes very long, time. Neither one medical specialty cannot do without knowledge fundamentals of medical genetics, since hereditary diseases affect all organs and systems of human organs .The key to medical genetics is development of methods for diagnosing, treating and preventing human hereditary diseases. Etiology of hereditary diseases Etiological factors of hereditary diseases are mutations (changes) in the hereditary material Mutations affecting the entire chromosome set or individual chromosomes in it (polyploidy and aneuploidy), as well assections of chromosomes (structural rearrangements - deletions, inversions, translocations, duplications, etc.) lead to the development chromosomal disea~~ In chromosomal diseases, the balance of the gene set is disturb
ABSTRACT
Tashkent Medical Academy Integration of Science, Education and Practice in Modern Psychology and Pedagogy: Problems and Solutions
Volume 4 | TMA Conference | 2023 Zamonaviy psixologiya, pedagogikada fan, ta'lim va amaliyot integratsiyasi: muammo va yechimlar
which can lead toto intrauterine death of embryos and fetuses, congenital malformations and other clinical manifestations. The more chromosomal material is involved in the mutation, the earlier the disease manifests itself and the more significant the impairment in the physical and mental development of the individual. About 1000 types of chromosomal disorders are known in a person. Chromosomal diseases are rarely transmitted from parents to children, mostly it is a randomly arisen new mutation. But about 5% of people are carriers of balanced changes in chromosomes, therefore, with infertility,stillbirths, recurrent miscarriage, or the presence of in the family of a child with a chromosomal pathology, it is necessary to examine the chromosomes of each of the spouses . Genetic diseases are diseases caused by changes structure of the DNA molecule (gene mutations).
Monogenic diseases (actually hereditary diseases) - phenotypically gene mutations - can manifest themselves in molecular, cellular, tissue, organand organism levels.Polygenic diseases (multifactorial) - diseases with a hereditary predisposition due to interaction of several (or many) genes and factors environment.
The contribution of hereditary and congenital diseases to infant and child mortality in developed countries (according to WHO) is large Among the main causes of death under the age of 1 year, the proportion of perinatal factors is 28%, congenital and hereditary diseases - 25%, sudden child death syndrome - 22%, infections - 9%, others - 6%. Leading cause of death between the ages of 1 years to 4 years are accidents (31%), congenital and hereditary diseases (23%), tumors (16%), infections (11%), others (6%).A significant role of hereditary predisposition in the occurrence of widespread diseases has been proven.(disease of the stomach and duodenum, essential hypertension, coronary heart disease, ulcerative psoriasis, bronchial asthma, etc.). Therefore, for prevention and treatment of these diseases, it is necessary to know the mechanisms of interaction of environmental and hereditary factors in their occurrence and development. Hereditary diseases for a long time did not respond to treatment, and the only method of prevention wasrecommendation to refrain from childbearing. These times passed. Modern medical genetics has armed clinicians with methods of early, presymptomatic (preclinical) and even prenatal diagnosis of hereditary diseases. Methods of preimplantation (before embryo implantation) are being intensively developed and are already being used in some centers diagnostics. Now there is a harmonious system for the prevention of hereditary diseases: medical genetic counseling, preconcep prophylaxis, prenatal diagnosis, mass diagnostics in newborns
Tashkent Medical Academy Integration of Science, Education and Practice in Modern Psychology and Pedagogy: Problems and Solutions
Volume 4 | TMA Conference | 2023
Zamonaviy psixologiya, pedagogikada fan, ta'lim va amaliyot integratsiyasi: muammo va yechimlar
y
hereditary metabolic diseases amenable to dietary and medicinal correction, clinical examination of patients and their families. The introduction of this system ensures a reduction in the frequency of birth of children with congenital malformations and hereditary diseases by 60-70%. Monogenic diseases (MB), or gene (as they are called for abroad) diseases. MB is based on single genes or point mutations. MB make up a significant share hereditary pathology and today there are more than 4500 diseases. According to the literature, in different countries they are detected in 30-65 children per 1000 newborns, which is 3.0-6.5%, and in the structure of total mortality of children up to 5 years, they account for 10-14%. Diseases are numerous and differ in the expressed clinical polymorphism. Genetic diseases are most often manifested by hereditary metabolic defects - fermentopathy. Same gene disease can be caused by different mutations. For example, more than 200 such genes are described in the cystic fibrosis gene. mutations, in the phenylketonuria gene - 30. In some cases mutations in different parts of the same gene can lead to different diseases (for example, mutations in the RET oncogene).
Pathological mutations can be realized in different periods of ontogeny. Most of them manifest themselves in utero (up to 25% of all hereditary pathology) and in prepubertal age (45%). About 25% of pathological mutations manifest themselves in puberty and adolescence, and only 10% monogenic diseases develop over the age of 20 years. Substances that accumulate as a result of the absence or decrease in the activity of enzymes either themselves have a toxic effect, or are included in the chain of secondary metabolic processes that produce toxic products. Overall frequency of gene diseases in human populations is 2-4%. Genetic diseases are classified: according to the types of inheritance (autosomal dominant, autosomal recessive, X-linked dominant, etc.); according to the nature of the metabolic defect - hereditary metabolic diseases - NBO (diseases associated with impaired amino acid, carbohydrate, lipid, mineral metabolism, nucleic acid metabolism acids, etc.); depending on the system or organ, the most involved in the pathological process (nervous, ocular, skin, endocrine, etc.).
NBOs include:
> diseases of amino acid metabolism (PKU, tyrosinosis, alkaptonuria, leucinosis, etc.);
> diseases of carbohydrate metabolism (galactosemia, glycogenosis, mucopolysaccharidoses);
Tashkent Medical Academy Integration of Science, Education and Practice in Modern Psychology and Pedagogy: Problems and Solutions
Volume 4 | TMA Conference | 2023
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y
> diseases of porphyrin and bilirubin metabolism (Gilbert syndrome, Crigler-Najjar syndrome, porphyria, etc.);
> diseases of the biosynthesis of corticosteroids (adrenogenital syndrome, hypoaldosteronism, etc.);
> diseases of purine and pyramidal metabolism (orotic aciduria, gout, etc.);
> lipid metabolism diseases (essential familial lipidosis, gangliosidoses, sphingolipidoses, cerebrosidoses and etc.);
> erythrone disease (Fanconi anemia, hemolytic anemia, deficiency of glucose-6-phosphate dehydrogenase, etc.);
> diseases of metal metabolism (Wilson-Konovalov's disease, Menkes, familial periodic paralysis, etc.);
> diseases of the transport systems of the kidneys
> (de Tony-Debre disease Fanconi, tubulopathies, vitamin D-resistant rickets,
etc.).
Chromosomal diseases (chromosomal syndromes)
Complexes of multiple congenital malformations are called development caused by numerical (genomic mutations) or structural (chromosomal aberrations) changes in chromosomes, visible in a light microscope. Chromosomal aberrations and changes in the number of chromosomes, as well as gene mutations, can occur at different stages of an organism's development. If they arise in the gametes of the parents, then the anomaly will be observed in all cells of the developing organism (complete mutant). If an anomaly occurs in the process of embryonic development during the crushing of the zygote,the fetal karyotype will be mosaic. Mosaic organisms may contain several (2, 3, 4 or more) cell clones with different karyotypes. This phenomenon may be accompanied by mosaicism in all or in individual organs and systems with a small number of abnormal cells, phenotypic manifestations may not be detected. Etiological factors of chromosomal pathology are all types of chromosomal mutations (chromosomal aberrations) and some genomic mutations (changes in the number of chromosomes). In humans, there are only 3 types of genomic mutations: tetraploidy, triploidy and aneuploidy. Of all options aneuploidy, only trisomy for autosomes, polysomy for sex chromosomes (tri-, tetra- and pentasomy) are found, and of monosomy, only monosomy X.All types of chromosomal mutations have been found in humans: eletions, duplications, inversions and translocations. A deletion (lack of a site) in on the homologous chromosomes means partial monosomy in
Tashkent Medical Academy Integration of Science, Education and Practice in Modern Psychology and Pedagogy: Problems and Solutions
Volume 4 | TMA Conference | 2023
Zamonaviy psixologiya, pedagogikada fan, ta'lim va amaliyot integratsiyasi: muammo va yechimlar
area, and duplication (doubling of the site) - partial trisomy.Chromosomal disorders in newborns occur with a frequency of approximately 2.4 cases per 1000 births. Most chromosomal abnormalities (polyploidy, haploidy, trisomy for large chromosomes, monosomy) are incompatible with life - embryos and fetuses are eliminated from the body mothers mostly in early pregnancy.Chromosomal abnormalities also occur in somatic cells with a frequency of about 2%. Normally, these cells are eliminated immune system if they manifest themselves as foreign. However, in some cases (activation of oncogenes), chromosomal abnormalities can be the cause of malignant growth. For example, a translocation between chromosomes 9 and 22 causes chronic myeloid leukemia. Common to all forms of chromosomal diseases is multiplicity of lesions. These are craniofacial lesions, congenital malformations of organ systems, delayed intrauterine and postnatal growth and development, mental retardation, impaired functions of the nervous, immune and endocrine systems.
Despite great advances in the improvement of cytogenetic, biochemical and molecular methods in the study of the etiology and pathogenesis of NZ is still the main symptomatic treatment remains, which differs little from the treatment of any other chronic diseases. But still currently in the arsenal of geneticists is many means of pathogenetic treatment; Firstly this applies to hereditary metabolic diseases (NBO). Clinical manifestations in NBO are the result of violations in the chain of transformations (metabolism) of products (substrates) in the human body; gene mutation leads to defective work of enzymes and coenzymes. Pathogenetic therapydesigned for approximately 30 NBOs. All pregnant women with altered levels of alpha-fetoprotein in the blood need additional examination. The content of alpha-fetoprotein in biological fluids increased with multiple malformations, spinal hernia, hydrocephalus, anencephaly, malformations development of the gastrointestinal tract and defects in the anterior abdominal wall, hydronephrosis and kidney agenesis, as well as placental insufficiency, intrauterine growth retardation, multiple pregnancy, preeclampsia, Rhesus conflict and viral hepatitis B.In cases of chromosomal diseases in the fetus (for example, Down's disease) or the presence of diabetes mellitus in a pregnant woman 1 type, on the contrary, the concentration of alpha-fetoprotein in the blood pregnant women is reduced.
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Tashkent Medical Academy Integration of Science, Education and Practice in Modern Psychology and Pedagogy: Problems and Solutions
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Zamonaviy psixologiya, pedagogikada fan, ta'lim va amaliyot integratsiyasi: muammo va yechimlar
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