HEREDITARY DISEASES — the diseases of the person caused chromosomal and genovariations. Quite often the terms «hereditary disease» and «inborn disease» are used as synonyms, however inborn diseases (see) are the diseases which are available at the birth of the child, they can be caused by both hereditary, and exogenous factors (e.g., the malformations connected with impact on an embryo of radiation, chemical connections and pharmaceuticals, and also pre-natal infections).
N. and inborn malformations are the reason of hospitalization of children almost in 30% of cases, and taking into account diseases of the unknown nature, to-rye can be substantially connected with genetic factors, this percent is even higher. However not all N. carry to inborn as many of them are shown after the period of a neonatality (e.g., the chorea of Gentington develops after 40 years). As a synonym of the term «hereditary diseases» it is also not necessary to consider the term «family diseases» since family diseases can be caused not only hereditary factors, but also living conditions or professional traditions of a family.
N. are known to mankind for a long time. A wedge, their studying began at the end of 18 century. In 1866 M. Florinsky in the book «Improvement and Degeneration of the Human Race» gave the correct assessment of value of the environment in formation of ancestral features, an adverse effect on posterity of closely related marriages, described inheritance of a row patol, signs (a surdomutism, a pigmental retinitis, albinism, a labium leporium, etc.). The English biologist F. Galton the first raised a question of heredity of the person as a subject of scientific studying. He proved genealogical method (see) and twin method (see) for studying of a role heredities (see) and the environment in development and formation of signs. In 1908 the English doctor of A. E. Garrod for the first time formulated the concept about hereditary «errors» of a metabolism, having approached thus studying of molecular bases of a row H.
In the USSR a big role in development of the doctrine about N. the person played Moscow medicobiological in-t of M. Gorky (later — Medicogenetic in-t), to-ry functioned from 1932 to 1937. In are in-those cytogenetic researches were conducted and diseases with hereditary predisposition were studied (a diabetes mellitus, a peptic ulcer of a stomach and duodenum, an allergy, a hypertension, etc.). The Soviet neuropathologist and the geneticist S. N. Davidenkov (1934) for the first time would establish existence of genetic heterogeneity of N. and reasons their wedge, polymorphism. He developed bases of a new type of medical aid — medicogenetic consultation (see. Medicogenetic consultation ).
Opening of the material carrier of heredity — DNA, mechanisms of coding (see. Genetic code ) allowed to understand value of mutations in N.'s development. L. Poling entered the concept «molecular diseases», i.e. the diseases caused by desequencing of amino acids in a polypeptide chain. Introduction to clinic of methods of unmixing of proteins, including and enzymes, identifications of products biochemical, reactions, achievements of cytogenetics, a possibility of mapping of chromosomes (see. Chromosome map ) allowed to find out the nature of a row H. Total number of famous N. by 70th 20 century reached 2 thousand.
Depending on a ratio of a role of hereditary and exogenous factors in an etiology and a pathogeny of various diseases N. P. Bochkov suggested all diseases of the person to divide into four groups conditionally.
The first group of diseases of the person is N., at to-rykh manifestation patol, [[ MUTATIONS | mutations ]] (see) as etiol, the factor practically does not depend on the environment, edges are defined in this case only by expressiveness of symptoms of a disease. All treat diseases of this group chromosomal diseases (see) and gene N. with full manifestation, napr, a Down syndrome, Fenilketonuriya, hemophilia, glikozidoza, etc.
In the second group of diseases hereditary changes also are etiol, a factor, however for manifestation of mutant genes (see. Penetrance of a gene ) the corresponding influence of the environment is necessary. Carry gout, nek-ry forms of a diabetes mellitus to such diseases, a hyper lipoprotein-my (see. Lipoproteids ). Similar diseases are more often shown at continuous influence of adverse or harmful environmental factors (physical or intellectual overfatigue, disturbance of food, etc.). These diseases can be carried to group of diseases with hereditary predisposition; for one of them the environment has bigger, for others — smaller value.
In the third group of diseases etiol, a factor is the environment, however the frequency of developing of diseases and weight of their current depend on hereditary predisposition. The hypertension and atherosclerosis, a peptic ulcer of a stomach and duodenum, allergic diseases, many malformations, certain forms of obesity belong to diseases of this group.
The fourth group of diseases is connected only with influence of adverse or harmful environmental factors, heredity in their emergence practically does not play any role. Carry injuries, burns to this group, acute inf. diseases. However genetic factors can exert a certain impact on a current patol, process, i.e. on rates of recovery, transition of acute processes in chronic, development of a decompensation of functions of the struck bodies.
Roberts and soavt. (1970) counted that among the reasons of child mortality genetic components of a disease are defined in 42% of cases, including 11% of children would die of actually N. and 31% — from the acquired diseases which developed on an adverse hereditary background.
The 20 century, known by 70th, N. subdivide into three basic groups.
1. Monogenic diseases: a) on a mode of inheritance — autosomal domi-nantnye, autosomal and recessive, linked to a floor; on phenotypical manifestation — enzymopathies (a disease of a metabolism), including the diseases caused by disturbance of DNA repair, the diseases caused by pathology of structural proteins, an immunopathology, including disturbances in system of a complement, disturbance of synthesis of transport proteins, including blood proteins (a hemoglobinopathy, Wilson's disease, an atransferrinemiya), pathology of coagulant system of blood, pathology of transfer of substances through cellular membranes, disturbances of synthesis of peptide hormones.
2. Polygenic (multifaktorial-ny) diseases or diseases with hereditary predisposition.
3. Chromosomal diseases: polyploidies, aneuploidies, restructurings of chromosomes.
Monogenic diseases are inherited in full accordance with Mendel's laws (see. Mendel laws ). Famous N.' most. it is caused by a mutation of structural genes; an opportunity etiol, is still proved to a role of mutations of regulator genes at nek-ry diseases only indirectly.
Autosomal and dominant type inheritance (see) it is characteristic of N., to-rykh disturbance of synthesis of structural proteins of a pla of the proteins performing specific functions is the cornerstone (e.g., hemoglobin). At the same time to ooze of inheritance action of a mutant gene is shown practically always. Sick boys and girls are born with an identical frequency. The probability of a course of a disease in posterity makes 50%. One of parents of the sick child is surely sick. On autosomal dominantly type are inherited Alporta syndrome (see), Marfana syndrome (see), Albright's disease (see. Pseudohypoparathyroidism ), a hemorrhagic teleaigiektaziya of Osler (see. Oslera — Randyu a disease ), hemochromatosis (see), a hyperbilirubinemia, Gilbert's syndrome — Meylengrakhta, a syndrome the Cudgel — Johnson (see. Hepatoses ), dysostoses (see), Elersa — Danlosa a syndrome (see. Desmogenez imperfect ), neurofibromatosis (see), otosclerosis (see), paroxysmal mioplegiya (see), thalassemia (see), tuberous sclerosis (see), a disease Sterdzha (Shturge) — Weber (see. Entsefalotrigeminalny angiomatosis ), elliptotsitoz (see. Hemolitic anemia ), etc.
At an autosomal and recessive mode of inheritance the mutant gene is shown only in a homozygous state. Sick boys and girls are born with an identical frequency. The probability of the birth of the sick child makes 25%. Parents of sick children can be healthy phenotypical, but are heterozygous carriers of a mutant gene. The autosomal and recessive mode of inheritance is more characteristic of diseases, at to-rykh function of any enzyme (or any enzymes) — so-called is broken. enzymopathies (see).
The recessive inheritance linked to X-chromosome is that action of a mutant gene is shown only at a XY set of gonosomes, i.e. at boys. The probability of the birth of the sick boy at mother — the bearer of a mutant gene — makes 50%. Girls are almost healthy, but a half of them is bearers of a mutant gene (so-called conductors). Parents are healthy. Often the disease is found in sons of sisters of a proband or its cousins on the maternal line. The sick father does not transmit a disease to sons. This mode of inheritance is characteristic of the progressing muscular dystrophy like Dyushenn (see. Myopathy ), hemophilias And yes In (see. Hemophilia ), Lesh's syndrome — Naykhana (see. Gout ), Gunter's diseases (see. Gargoilizm ), Fabri of a disease (see), genetically caused insufficiency of a glyukozo-6-phosphate-dehydrogenase (nek-ry forms).
The dominant inheritance linked to X-chromosome is that action of a dominant mutant gene is shown in any set of gonosomes (XX, XY, H0, etc.). Display of a disease does not depend on a floor, however proceeds at boys more hard. Among children of the sick man in case of inheritance of this kind all sons are healthy, all daughters are struck. Sick women give the changed gene to a half of sons and daughters. This mode of inheritance is traced at phosphate diabetes.
On phenotypical manifestation to monogenic N. belong enzymopathies, to-rye make the most extensive and best of all the studied group H. Primary defect of enzyme is deciphered approximately at 150 enzymopatiya. The following reasons of enzymopathies are possible: a) enzyme is not synthesized absolutely; b) in a molecule of enzyme the sequence of amino acids is broken, i.e. its primary structure is changed; c) the coenzyme of the corresponding enzyme is absent or is incorrectly synthesized; d) activity of enzyme is changed in connection with anomalies in other fermental systems; e) blockade of enzyme is caused by genetically determined synthesis of the substances inactivating enzyme. Enzymopathies are in most cases inherited on autosomal recessively type.
The mutation of a gene can cause disturbance of protein synthesis, performing plastic (structural) functions. Disturbance of synthesis of structural proteins — a probable cause of such diseases, as osteodysplasias (see) and bone formation imperfect (see), Elers's syndrome — Danlosa. There are data on a certain role of these disturbances in a pathogeny of hereditary nefritopodobny diseases — Alport's syndrome and a family hamaturia. As a result of anomalies in structure of proteins basal, and also cytoplasmic membranes the fabric hypoplastic dysplasia — histologically the found immaturity of fabric structures develops. It is possible to assume that the dysplasia of fabric can come to light not only in kidneys, but also in any other bodies. Pathology of structural proteins is characteristic of N.'s most., inherited on autosomal dominantly type.
In a stage of studying there are diseases, to-rykh insufficiency of mechanisms of recovery of the changed molecule DNA is the cornerstone. Disturbance of mechanisms of DNA repair is established at to a xeroderma pigmental (see), Blum's syndrome (see. Poikiloderma ) and Kokkeyn's syndrome (see. Ichthyosis ), an ataxy teleangiectasia (see. Ataxy ), Down diseases (see), Fankoni's anemias (see. Hypoplastic anemia ), to a system lupus erythematosus (see).
Genovariation can lead to development of immunodeficient diseases (see. Immunological insufficiency ). In the most severe forms proceeds agammaglobulinemia (see), especially in combination with an aplasia of a thymus. In 1949. L. Poling and sotr. established that the reason of abnormal structure of hemoglobin at drepanocytic anemia (see) replacement in a molecule of hemoglobin of the rest glutaminic to - you for the rest of valine is. Later it was established that this replacement was result of genovariation. It served as the beginning of intensive researches hemoglobinopathies (see).
A number of mutations of the genes controlling synthesis of blood-coagulation factors is known (see. Coagulant system of blood ). Genetically determined disturbances of synthesis of anti-hemophilic globulin (the VIII factor) lead to development of hemophilia And. At disturbance of synthesis of a thromboplastic component (a factor of IX) the Cristmas disease develops. The shortcoming of the predecessor of thromboplastin is the cornerstone of a pathogeny of hemophilia of Page.
Genovariations can be a cause of infringement of transport of various connections (organic compounds, ions) through cellular membranes. Hereditary pathology of transport of amino acids in intestines and kidneys, the sprue of glucose and a galactose are most studied, effects of disturbance potassium - sodium «pump» of a cell are studied. An example of the disease caused by hereditary defect of transport of amino acids is Cystinuria (see), clinically shown nefrolitpazy and symptoms of pyelonephritis. The classical Cystinuria is caused by disturbance of transport of a row diamgshokarbonovy to - t (arginine, a lysine) and cystine through cellular membranes both in intestines, and in kidneys, and meets less often than a hyper cystinuria, edges is characterized only by disturbance of transfer of cystine through cellular membranes in kidneys, at the same time the nephrolithiasis develops seldom. The seeming contradictions of literary data on the frequency of a hyper cystinuria as biochemical, a sign and a cystinuria as diseases are explained by it.
Pathology of a reabsorption of glucose in renal tubules — a renal glucosuria is connected with dysfunction of membrane is white kov-carriers or with defects in system of provision of energy of processes of active transport of glucose; it is inherited on autosomal dominantly type. Disturbance of a reabsorption of bicarbonates in proximal departments of nephron or disturbance of secretion of hydrogen ions cells of a renal epithelium of distal departments of nephron is the cornerstone of two types of renal canalicular acidosis (see. Laytvuda — Albright a syndrome ).
The mucoviscidosis can be also carried to diseases, in a pathogeny to-rykh an essential role plays disturbance of transmembrane transfer and secretory function of excretory glands. Diseases are known, at to-rykh function of the membrane mechanisms responsible for maintenance of a normal concentration gradient of ions is broken To + and Mg 2+ in and out of a cell that is clinically shown by periodic attacks of a tetany.
Polygenic (multifactorial) diseases or diseases with hereditary predisposition are caused by interaction of several or many genes (polygenic systems) and environmental factors. The pathogeny of diseases with hereditary predisposition, despite their prevalence, is studied insufficiently. Deviations from normal options of a structure of structural, protective and fermental proteins can define existence of numerous diathesis at children's age. Search of phenotypical markers of genetic predisposition to a certain disease is of great importance; e.g., allergic diathesis can be diagnosed on the basis of the increased content in blood of immunoglobulin E and the raised excretion of minor metabolites of tryptophane with urine. Markers of genetic predisposition to a diabetes mellitus (the tolerance test to glucose, definition of immunoreactive insulin), constitutional exogenous to obesity, a hypertension are defined biochemical, (giperlipoproteinemiya). Success in studying of interrelation between blood groups of AB0 is achieved (see. Group-specific substances ), system of a gaptoglobin, HLA antigens and diseases. It is established that for persons with a fabric haplotype of HLA-B8 the risk of a disease hron, hepatitis, a Gee's disease and a myasthenia is high; for persons with a haplotype of HLA-A2 — hron. glomerulonephritis, leukosis; for persons with a haplotype of HLA-DW4 — a pseudorheumatism, for persons with a haplotype of HLA-A1 — an atopic allergy. Communication with system of histocompatability of HLA is found approximately for 90 diseases of the person, many from to-rykh are characterized by immune disturbances.
Chromosomal diseases are subdivided into the anomalies caused by changes of quantity of chromosomes (a polyploidy, an aneuploidy) or restructurings of chromosomes — deletions (see), inversions (see), translocations (see), duplications (see). The chromosome mutations which arose in formative cells (gametes) are shown in so-called full forms. Not discrepancy of chromosomes and structural changes which developed on early reduction stages of a zygote lead to development mosaicism (see).
The risk of repeated manifestation of the majority of chromosomal diseases in a family does not exceed 1%. The exception is made by syndromes of a translocation, at to-rykh the size of repeated risk reaches 30% and more. The probability of emergence of aberation chromosomes sharply increases at women 35 years are more senior.
Wedge, N.'s classification. it is constructed by the organ and system principle and does not differ from classification of the acquired diseases. According to this classification would allocate N. the nervous and endocrine systems, easy, cardiovascular system, a liver, went. - kish. path, kidneys, sistvkhma of blood, skin, ear, nose, eyes, etc. Such classification is conditional since N.'s most. it is characterized by involvement in patol, process of several bodies or systemic lesion of fabrics.
Monogenic N.' frequency. fluctuates at different ethnic groups of the population in different geographical zones. It clearly is traced on the example of concentration of a sickemia and a thalassemia in geographical regions with high exposure of the population to a disease of malaria. Prevalence of diseases with hereditary predisposition substantially defines balanced polymorphism (see). Concentration of a number of monogenic N. can be also connected with this phenomenon. (Fenilketonuriya, mucoviscidosis, hemoglobinopathies, etc.). Features of geographical distribution of N. depend also on drift of genes and effect of the ancestor. Within only 200 years in South Africa in such way genes of a porphyria extended. Concentration of mutant genes in limited territories is connected with the frequency of kinship marriages, especially high in isolates (see).
In Western Europe and in the USSR the most widespread N. exchange are a mucoviscidosis (see) — 1: 1200 — 1: 5000; Fenilketonuriya (see) — 1: 12000 — 1: 15000; galactosemia (see) — 1: 20000 — 1: 40000; The Cystinuria — 1: 14000; histidinemia (see) — 1: 17000. Frequency of giperlipoproteinemiya (including poligenno the inherited forms) reaches 1: 100 — 1: 200. To often found N. exchange it is necessary to carry hypothyroidism (see) — 1: 7000; malabsorption syndrome (see) — 1: 3000; adrenogenital syndrome (see) — 1: 5000 — 1: 11000, hemophilia — 1: 10000 (boys are ill).
Such diseases as leucinosis, homocystinuria, meet rather seldom, their frequency 1: 200 000 — 1: 220 000. Frequency of considerable number H. exchange on purely technical restrictions (lack of express diagnostic methods, complexity of analytical researches for confirmation of the diagnosis) it is not established though it does not testify to their rarity.
Diseases with hereditary it is predisposed iy also have features of distribution in the different countries. So, according to Shands (Shands, 1963), the frequency of splitting of a lip and sky in England makes 1: 515, in Japan — 1: 333, at the same time spina bifida in England meets by 10 times more often than in Japan, and congenital dislocation of a hip is observed 10 times more often in Japan, than in England.
Frequency of all chromosomal diseases among newborns, according to Kebak (M. M. of Kaback, 1978), makes 5,6:1000, at the same time all types of aneuploidies, including mosaic forms, make 3,7: 1000, trisomies on autosomes and restructurings — 1,9: 1000. A half of all cases of restructurings of chromosomes is represented by family cases, all trisomies represent sporadic cases, i.e. the investigation of again arisen mutations. According to Polani (P. Polani, 1970), apprx. 7% of all pregnancies are complicated by aberation chromosomes of a fruit, to-rye in most cases lead to spontaneous abortions. Frequency of aberation chromosomes at premature children is 3 — 4 times higher, than at full-term and makes 2-2,5%.
Diagnosis of a row H. does not represent essential difficulties and is based on the data obtained as a result of all-clinical inspection (e.g., a Down syndrome, hemophilia, a gargoilizm, an adrenogenital syndrome, etc.). However in most cases at their diagnosis arise seryeznye difficulties because many N. on a wedge, to manifestations are very similar to the acquired diseases — so-called phenocopies of N. Existence of a number phenotypical of similar, but heterogeneous diseases in the genetic relation is known (e.g., Marfan's syndrome and a homocystinuria, a galactosemia and Lowe's syndrome, phosphate diabetes and renal canalicular acidosis). All cases atypically proceeding or hron, diseases demand the kliniko-genetic analysis. On N. can specify existence specific a wedge, signs. Among them special diagnostic value symptoms of a dysplasia — an epikant can have, a hypertelorism, saddle Nov, features of a structure of the person (the «bird's», «doll», oligomimichny person, etc.), skulls (a dolichocephalia, a brachycephaly, a plagiotsefaliya, a «buttock» shape of a skull, etc.), an eye, teeth, extremities, etc.
At suspicion on N. genetic inspection of the patient begins with obtaining detailed kliniko-genealogical data on the basis of poll on the state of health of the immediate and remote family, and also special inspection of family members that allows to make a medical family tree of the patient and to define the nature of inheritance of pathology (see enealogichesky method ). Auxiliary (and in some cases and solving) diagnostic value various paraclinic methods, including biochemical, and cytochemical have, researches, a submicroscopy of cells etc. The diagnostic methods of disbolism based on use are developed biochemical, chromatography (see), electrophoresis (see), ultracentrifuging (see) etc. Apply methods of definition of activity of these enzymes in plasma and blood cells to diagnosis of the diseases caused by insufficiency of enzymes, in the material received at a biopsy of bodies in culture of fabrics.
Carrying out biochemical researches at N. exchange in some cases metabolism to-rykh as assume demands use of load tests by connections, it is broken. Expansion of diagnostic opportunities is connected with development and practical use of methods of allocation, cleaning and definition physical. - chemical characteristics, including and kinetic, enzymes of blood cells and fabric cultures at N.
However difficult analytical methods cannot be used for mass inspections. In this regard conduct two-stage examination using simple on-lukolichestvennykh methods at the initial stage and at positive takes of the first stage — analytical methods; these programs received the name sifting or screening (see).
For semi-quantitative determination of content of amino acids, a galactose and some other connections in blood most often use microbiological methods (see. Guthrie method ). In a number of laboratories on a nerve a stage apply a thin-layer chromatography. In certain cases use radiochemical methods, napr, for identification of a hypothyroidism at newborns. Implementation of methods automatic biochemical, the analysis would facilitate carrying out mass inspection of children on N.
In many countries mass screening is carried out, at Krom all newborns or children of more advanced age, and so-called selection screening when only children from specialized institutions (somatic, psychoneurological, ophthalmologic and other hospitals) are inspected are inspected.
Mass inspections of the children's contingents (especially newborn) allow to reveal inherited disorders of exchange in a preclinical stage when the dietotherapy and the corresponding pharmaceuticals are capable to prevent development of heavy disability completely.
Development of new methods of cultivation of cells, biochemical, and cytogenetic researches would make possible prenatal diagnosis of N., including all chromosomal diseases and diseases linked to X-chromosome and also a number of inherited disorders of a metabolism. Results of a research can serve as the indication for abortion or an initiation of treatment of anomalies of exchange in the pre-natal period. Prenatal diagnosis of N. it is shown when restructuring of chromosomes is found in one of parents (a translocation, inversion) when the age of pregnant women exceeds 35 years and when in a family are traced it is prepotent the inherited diseases or there is a high risk of emergence of recessive hereditary diseases — autosomal or linked to X-chromosome.
Amniocentesis (see) it can be combined with amnio-and a fetoskopiya (see. Amnioskopiya ). Aberation chromosomes in culture of cells of an amniotic fluid indicate pathology of the developing fruit, especially at elderly mother, and also in the presence in a family of the child with chromosomal pathology or multiple inborn defects, the balanced translocation at one of parents, usual abortions in the anamnesis at mother.
Biochemical, to researches, hl. obr. to definition of activity of a number of enzymes, subject also the cells which are grown up in culture that allows to find a number of the diseases caused by disturbance of lipid metabolism, mucopolysaccharides, carbohydrates, amino acids nucleinic to - t — only more than 70 diseases. Diagnostic methods of a disease Teja — the Saxophone, Lesh's syndrome — Naykhana, nek-ry mukopolisakharidoz are the most developed.
For diagnosis of most of N. difficult methods biochemical, researches, performance to-rykh perhaps only in the special centers are required. Development of micro technical methods (mikrospektro-photometry, mikroflyuorimetriya and tracer techniques) allowed to reduce terms of cultivation of cells of an amniotic fluid to 7 days since the analysis requires only 10 — 100 cells. For antenatal diagnosis use also a X-ray analysis, an electrocardiography of a fruit.
One of the most widespread methods of pathogenetic treatment of N. exchange the dietotherapy is. Carrying out a dietotherapy demands strict observance of a number of conditions: the exact diagnosis of anomaly of the exchange excluding the mistakes connected with existence phenotypical of similar syndromes; the maximum adaptation of a diet to requirements of the growing organism; careful clinical and biochemical control.
Possibilities of dietary correction of exchange of phenylalanine at a fenilketonuriya are fullestly studied. For dietary correction of a galactosemia special drugs are created: soyaval, nutramigen (from beans of soy), delactosed drug enpit. Drugs like en pita with success would be used at other N.' treatment. (Marfan's syndrome, Laurence's syndrome — Muna — Bidlya). Also special diets for treatment of a histidinemia, a homocystinuria, a ketoaciduria, etc. are offered.
Search of methods of treatment of patients with hereditary enzymopathies continues. Replacement therapy at enzymopathies is limited to rather small number H., hl. obr. diseases went. - kish. a path, to-rykh insufficiency of the enzymes participating in processes of splitting and absorption is the cornerstone (a mucoviscidosis, deficit of disaccharidases, trypsinogen, etc.). The gastric juice, pepsin, trypsin, Pancreatinum are long since applied in medicine, there passes the wedge, tests a method of administration of lactase, barmy invertase, gamma amylase from mold fungi at disturbances of absorption of lactose, sucrose and starch.
Replacement therapy by the drugs of gamma-globulin enriched with antibodies or classes of immunoglobulins is carried out at treatment of the hereditary immunopatiya connected with deficit of immunoglobulins. For treatment of hereditary endocrine diseases enter corticosteroids (at an adrenogenital syndrome), Thyreoidinum (at a hypothyroidism), insulin (at a diabetes mellitus), etc.
The main obstacle at treatment of hereditary enzymopathies by method of administration of missing enzymes, i.e. by method of replacement therapy, are immune responses. New opportunities in this direction are opened by use of artificially created lipidic particles — liposomes (see). Cells of fabrics take liposomes, under the influence of cellular lipases (see) the cover of a liposome collapses, and enzyme shows the action in a cell. As a protective shell for the enzyme entered with the therapeutic purpose use also shadows of erythrocytes of the patient, nylon capsules. A recent trend in N.'s treatment. development of methods of induction of synthesis of enzymes by means of chemical drugs and hormones is. It is established that barbiturates induce synthesis of a glyukuroniltransferaza — the enzyme necessary for formation of glucuronides of bilirubin (so-called direct bilirubin), steroid hormones and some other connections. Substantial increase of activity of a glyukuroniltransferaza under the influence of phenobarbital at patients with Krig-ler's syndrome — Nayara is noted, to-ry it is characterized by a sharp hyperbilirubinemia in connection with hereditary insufficiency of this enzyme. Glucocorticoids activate synthesis of a glyukozo-@-phosphate-dehydrogenase and can be used at treatment of a glycogenous disease of the I type (a disease to Awnless wheat) for the purpose of the prevention of hypoglycemic states and decrease in intensity of accumulation of a glycogen in fabrics (see. Glycogenoses ). The inducing influence of corticosteroids on synthesis and maturing of fermental systems of intestines, in particular disaccharidases is established. Oestrogenic hormones cause increase of concentration of ceruloplasmin in blood therefore they are used at treatment hepatocerebral dystrophy (see).
Can induce synthesis of enzymes also vitamins, and it is especially noticeable at so-called vitaminozavisimy states, to-rye are characterized by development hypo - or avitaminosis not in connection with limited intake of polyneuramins an organism, and as a result of disturbance of synthesis of specific transport proteins or apoenzymes (see. Enzymes ). Efficiency of high doses of rat anti-acrodynia factor is well-known (from 100 mg and above in days) at so-called piridoksinzavisimy states and diseases (a tsistatio-ninuriya, a homocystinuria, family hypochromia anemia, and also Knapp's syndrome — Komrovera, Hartnup's disease, nek-ry forms of bronchial asthma). High doses of vitamin D (to 50 000 — 200 000 ME a day) were effective at hereditary rakhitopodobny diseases (phosphate diabetes, de Tony's syndrome — Debra — Fankoni, renal canalicular acidosis). Redoxon in doses to 1000 mg a day is applied at treatment an alkaptonuria High doses of vitamin A appoint the patient with syndromes Gurler and Gunter (mukopolisakharidoza). Improvement of a condition of patients of a mukopolisakharidozama under the influence of Prednisolonum is noted.
At N.'s treatment. use the principle of suppression of exchange reactions, however for this purpose it is necessary to have clear idea of influence of chemical predecessors or metabolites of the blocked reaction to functions of these or those systems.
Progress of a plastic and plastic surgery defined high performance of surgical treatment of hereditary and is congenital - day malformations. Implementation in practice of treatment of N. is perspective. methods of transplantation that will allow not only to replace the bodies which underwent irreversible changes but also to carry out changes for the purpose of the recovery of protein synthesis and enzymes which are absent at patients. Transplantation of immunocompetent bodies (a thymus, marrow) at treatment of different forms of hereditary insufficiency of immunity can be of great scientific and practical interest.
One of methods of treatment of N. purpose of the drugs connecting the toxic products which are formed as a result of blocking certain biochemical, reactions is. So, for treatment of hepatocerebral dystrophy (Wilson's disease — Konovalova) use the drugs forming soluble complex compounds with copper (Unithiolum, Penicillaminum). Complexons (see), specifically connecting iron, find application at treatment of hemochromatosis, and the complexons forming soluble complex compounds of calcium — at treatment of hereditary tubulo-patiya with a nephrolithiasis. At treatment of giperlipoproteinemiya apply holestiramin, to-ry connects cholesterol in intestines and interferes with its reabsorption.
In a stage of developments there is a search of levers, to-rymi can operate genetic engineering (cm).
Progress in prevention and N.'s treatment. first of all will be connected with creation of system of dispensary service of patients with hereditary diseases. On the basis of the order of the Minister of Health of the USSR No. 120 of October 31, 1979. «About a state and measures for further improvement of prevention, diagnosis and treatment of hereditary diseases» in the USSR 80 advisory offices on medical genetics will be organized, and also the centers for medikogenetichesky consultation, for hereditary pathology at children and on prenatal hereditary pathology are created.
Preservation and improvement of health of the population would depend substantially on N.'s prevention., especially important role of the genetics studying intimate mechanisms of all functions of an organism and their disturbances consists in it.
Separate hereditary diseases — see articles according to the name of diseases.
Modeling of hereditary diseases
Modelling of hereditary diseases consists in reproduction on animals or their bodies, fabrics and cells of hereditary diseases of the person (one patol, process or a fragment patol, process) for the purpose of establishment of an etiology and a pathogeny of these diseases and development of methods of their treatment.
Modeling played a big role in development of effective methods of treatment and prevention inf. diseases. At the beginning of the 60th 20 century as model objects for studying of hereditary pathology of the person began to use widely laboratory animals (mice, rats, rabbits, hamsters, etc.). Models H. the person can be also agricultural and wildings, both vertebrata, and invertebrates.
Possibility of modeling of N. first of all it is connected with existence at the person and of the animal homologous loci controlling similar processes of exchange of substances is normal also at pathology. And under the law of homologous series in hereditary variability formulated by N. I. Vavilov in 1922 than blizhe types in their evolutionary relationship are to each other located, shall be that at them a homologous genes more. At mammals pressed down processes substances, and also the structure and functions of bodies are similar therefore such animals would be of the greatest interest to N.'s studying. person.
From the point of view of an etiology, modeling on animals of those hereditary anomalies of the person is more justified, to-rye are caused by genovariations. It is explained by bigger probability of existence at the person and an animal homologous genes, than homologous sites (segments) or the whole chromosomes. Linin of animals, being carriers of the same hereditary anomaly which resulted from a mutation of a gene call mutant.
Indispensable condition of successful modeling of N. the person on animals Goma logicality or identity of diseases at the person and a mutant animal is what unambiguity or similarity of gene effects testifies to. N.'s modeling. the person can also be carried out on the isolated bodies, fabrics or cells. Partial modeling, i.e. reproduction not of all disease in tse-scrap but only one patol, process or even a fragment of such process is of great scientific and practical interest.
As a result of difficult interaction of products of many genes and existence of homeostatic mechanisms at the highest vertebrata final effects of different mutant genes can be in many respects similar. However it does not speak about uniformity of action of the genes causing anomalies, and similarity of a pathogeny yet. Therefore, there are more specific distinctions in primary, than in secondary or final effects of mutant genes. Therefore in most cases it is necessary to expect more expressed features in operation of genes at molecular or cellular level, than at the level of a complete organism. The aspiration of experimenters to find primary genetically caused aberration is explained by it in order that it is correct to understand a pathogeny of anomaly and accurately to differentiate clinically similar forms of diseases.
The possibility of use of a large number of animals at various stages of development patol, process is of great importance for specification and a specification of a pathogeny of anomalies and development of methods of their therapy and prevention.
Many mutant lines of the animals who are of interest as models H. are known. person. On nek-ry of them, in particular on lines of mice with hereditary obesity, immunodeficiency, diabetes, muscular dystrophy, a degeneration of a retina etc., intensive researches are conducted. The great value is attached to active searches at the animal anomalies similar to certain N. person. Animals, at to-rykh such anomalies are found, it is necessary to keep since they are of great interest to medicine.
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BB. E. Veltishchev; B. V. Konyukhov (gen).