This is a special, very large group of diseases, the detection and treatment of which is currently very actual problem due to their widespread prevalence and severe impairment of the physical and intellectual development of sick children. Tests to make a correct diagnosis are usually very complex and expensive. They can only be carried out in large specialized centers. Therefore, a special contingent of children has been identified for whom these studies need to be performed. These children include:

1. children who have a combination of mental retardation and visual impairment;
2. children who have mental retardation and periodically experience seizures;
3. children who have had changes in the color and odor of their urine since birth;
4. children whose mental retardation is combined with various skin lesions.

Below are the main diseases caused by disorders of amino acid metabolism in the body.

Phenylketonuria in children

Phenylketonuria is associated with a violation of the metabolism of amino acids, which are part of hormones thyroid gland and adrenal glands. As a result, the substance phenylalanine is formed in excess, which accumulates in the body and causes disorders associated mainly with damage to the brain and spinal cord. Although the disease is very common, it is almost never found among blacks and Jews. Girls and boys get sick equally often.

Very often, a sick child is born to completely healthy parents. This is due to the fact that the mother and father of the child, without knowing it, are carriers of the affected gene. The likelihood of a sick child appearing in a family where marriages take place between relatives increases very sharply.

Signs of phenylketonuria

They do not appear immediately after birth. Until 2-6 months of age, the child gives the impression of being quite healthy. Upon reaching the above age, when foods containing a “forbidden” amino acid appear in the diet, the child’s parents begin to notice that he has become lethargic, his physical activity, interest in toys and the people around me began to disappear. In some cases, the child, on the contrary, becomes restless, aggressive, often feels sick and vomits, and his skin becomes damaged. Subsequently, convulsive seizures occur. After the sixth month of life, a lag in physical and mental development becomes noticeable, and later there is a decrease in intelligence up to profound mental retardation, which is observed in more than half of all patients. There are, however, known cases of the disease progressing with preservation of normal intelligence. This fact is interpreted by experts as a consequence of the fact that disturbances in several different genes are responsible for the development of the disease, therefore the degree of severity of its symptoms can be very diverse. The picture of various neurological disorders in the disease is very rich.

The child’s physical development also suffers, but not as much; the body length is slightly reduced or normal. A slight decrease in the size of the head due to impaired growth of the skull bones is very typical; the teeth in such children begin to erupt at a very early age. late age. There are often malformations of the skeleton and internal organs. Very late, the child learns basic motor skills: crawling, sitting, standing. Subsequently, the sick child has a very peculiar body position and gait. When walking, his legs are widely spaced and slightly bent in knee joints, the head and shoulders are lowered. The steps are very small, the child sways from side to side. The position of a sick child when sitting is called the “tailor's position” - his legs are tucked towards the body as a result of increased muscle tension.

The appearance of a sick child is also very characteristic. His hair and skin are very light in color, as his body contains virtually no pigments. The eyes are light blue. excreted along with urine harmful products metabolism, as a result of which a peculiar, so-called “mouse” odor emanates from the child. Some patients develop seizures that resemble those of epilepsy. However, at a later age they disappear completely. In general, the spectrum of neurological disorders in phenylketonuria is very wide.

The most common symptoms observed are incoordination of movements, involuntary obsessive movements, shaking of fingers, convulsions in the various groups oh the muscles, their trembling. Reflexes in the arms and legs are significantly increased, and sometimes reflexes appear that are not normally observed. When the skin is irritated, a bright, for a long time persistent red or white color. The child often sweats, the tips of his fingers and toes are bluish in color. Very typical for phenylketonuria neurological disorders, known clinically as “Salaam’s seizures.” They manifest themselves in the form of periodic nods and bows, during which the child spreads his arms to the sides. During such attacks, the likelihood of injury is very high.

Numerous lesions are observed on the child’s skin, since due to the lack of pigments it is very vulnerable to the effects of sun rays. Lesions occur in the form of eczema, dermatitis, and often appear various rashes. Violations of internal organs are detected only in cases where there are birth defects their development. Arterial pressure in most cases it is at very low values. Function is often impaired gastrointestinal tract, constipation appears.

The severity of these manifestations directly related to the degree of metabolic disorder. Taken together, these signs are revealed only when the corresponding enzymes are completely absent in the body. With partial disruption of the enzymes, the manifestations of the disease are very diverse. As a rule, mental and mental disorders are combined to varying degrees. physical development child, neurological disorders and development characteristic manifestations after eating food containing large amounts of phenylalanine. There may be no manifestations at all, while the results of biochemical tests indicate the presence of a disease in the child.

These are the main manifestations of the form of the disease known as phenylketonuria type 1. In the second type of disease, the lag in intellectual development child, convulsive seizures often occur, the child is constantly restless, very excitable, and aggressive. Reflexes in the arms and legs are greatly increased, muscle tension is impaired, and complete paralysis of the muscles of the arms and legs occurs. The disease develops very quickly, and upon reaching the age of 2-3 years, the child dies.

There is also a type of disease of the third type, which in its characteristics is very similar to the second type, only much more severe mental retardation is revealed, a significant reduction in the size of the skull, and movements in the muscles of the arms and legs are more impaired.

In diagnosing the disease it is very great importance have different lab tests, especially the determination of phenylalanine levels in the blood. Nowadays they are increasingly used various methods genetic research.

Treatment of phenylketonuria in children

Consists of preventing complications associated with the disease. Full compensation for impaired metabolic processes is possible only if the correct diagnosis is made and adequate treatment is started in the shortest possible time, preferably before the birth of the child. From the very first days of life, all foods containing the “forbidden” amino acid are excluded from the child’s diet.

Only this event can achieve positive result and further normal development of the child. The diet must be strictly followed long time usually for at least 10 years.

All foods rich in protein substances are completely excluded from the child’s daily diet: meat, fish, sausages, eggs, cottage cheese, bakery products, cereals, legumes, nuts, chocolate, etc. Dairy products, vegetables and fruits are allowed to be consumed, but only in large quantities oh and taking into account the phenylalanine they contain.

It should be borne in mind that this amino acid is still essential in the body and the minimum requirements for it must be fully satisfied, otherwise it will lead to even more profound disturbances in the child’s development than the disease itself. Since most food products are contraindicated for a child, for a very long time he is doomed to eat only special products produced both abroad and in Russia. From the first days of a child’s life, it is forbidden to breastfeed; he should receive only formulas specially designed for these patients.

Diet for older children should only be compiled by a medical specialist. This takes into account not only the amount of phenylalanine in the product, but also the child’s age, height, weight, individual needs nutrients and energy.

Proteins enter the child’s body almost exclusively as part of the above specialized food products. The need for fats is satisfied mainly by creamy and vegetable oils. It is easier to provide the required amount of carbohydrates. For this purpose, the child is allowed to eat various fruits, vegetables, juices, sugar, and foods containing starch. Minerals and microelements enter the body almost exclusively through specialized products.

It should be remembered that their taste and smell can lead to a decrease in the child’s appetite. Some children develop nausea and vomiting after eating such food, and subsequently the child becomes capricious and refuses feedings. In these cases, it is possible to exclude the mixture from the diet for a short period of time. The baby's diet becomes much more varied after he reaches three months of life, when he is allowed to give fruit juices, after half a month, fruit puree is introduced. In another month, the time for introducing the first complementary foods in the form of vegetable puree or canned food, but without dairy products. At six months, a child can already eat porridge, but made from pureed sago or protein-free grains, jelly. Then the diet is expanded by introducing mousses.

In sick children in the second year of life, nutrition is very significantly different from that of healthy ones. IN daily ration the main place belongs to various vegetables and fruits. Apply special diets protein-free, which includes protein-free pasta, sago, protein-free cereals, corn starch, vegetable margarine, sour cream. Among products containing sugar, honey, jam, and jam are allowed.

Subject to an appropriate diet a necessary condition is constant monitoring of phenylalanine levels in the blood. If it increases, dietary recommendations need to be revised. When a disease is detected and its therapy has just begun, such studies must be carried out at least once a week, and in the future, when the child’s condition normalizes, at least once a month. When the child reaches an older age and his condition is stable, laboratory tests can be performed less frequently.

The diet can be gradually discontinued only when the child reaches the age of ten years. Subsequently, all these children are under the supervision of appropriate specialists in the clinic. Their mental and physical development is periodically assessed.

In addition to dietary recommendations, the child is prescribed drug treatment, which includes preparations of calcium, phosphorus, iron, vitamins, especially group B, drugs that improve the transmission of impulses in the nervous system, improve metabolic processes. A complex is assigned physical therapy. Work with a child with signs of mental retardation is carried out with the participation of experienced teachers.

For girls planning to have a pregnancy in the future, dieting is necessary until pregnancy and during it. These activities significantly increase the likelihood of having a healthy baby.

Forecast. It is completely determined by the timeliness of diagnosis and initiation of treatment. The second and third types of the disease are most unfavorable, since in them the diet turns out to be practically ineffective.

Histidinemia

It was first isolated as an independent disease in 1961. The metabolism of the amino acid histidine is disrupted, which mainly occurs in the skin and liver. The disease can be spread among different groups children with different frequencies.

Causes and mechanism of development of histidinemia

As a result of impaired breakdown of histidine, it accumulates in organs and tissues, mainly causing brain damage. There are several types of the disease, the main ones being:

1) the most common form in which amino acid metabolism is disrupted both in the skin and in the liver;

2) metabolic disorder only in the liver while it is preserved in the skin. The disease in this case progresses in more mild form, since the exchange is partially preserved;

3) incomplete metabolic disorder in the liver and skin. The disease is also relatively mild.

Signs of histidinemia

The first signs of the disease may appear in at different ages. They can occur both in a newborn child and during puberty. The disease is very diverse in its manifestations. The child may have a very deep delay mental development, but there may be no manifestations and may not arise during subsequent life. Violations mental development are detected in a child at a very early age. They manifest themselves in the form of seizures, loss of motor skills, and the child ceases to show interest in toys and people around him. In the future, mental retardation is always observed. It can be expressed to an insignificant extent, or it can reach almost extreme values. Mental disorders manifest themselves in the fact that the child very often experiences mood swings, most often he is excited and aggressive, his behavior and ability to concentrate on any subject are impaired. Most patients have speech impairment, often even with normal mental development.

It is characteristic that among sick children fair-haired with blue eyes than dark and brown. Therefore, doctors have difficulty differentiating the disease from phenylketonuria.

Main additional methods Biochemical laboratory tests help in diagnosis. Diagnosis is possible before the baby is born.

Treatment of histidinemia

As with other diseases associated with metabolic disorders, with histidinemia the most important method treatment is diet therapy. From birth, all foods containing the amino acid histidine are excluded from the diet. But since this substance is indispensable for child's body, then the minimum need for it must still be satisfied.

Fortunately, a product containing small amounts of histidine and recommended for children in infancy, is mother's milk. If this is not available, you can give special formulas for feeding, mare's milk and soy milk. Fruits and vegetables mainly contain carbohydrates, so they are “safe” foods and can be given in the same way as to healthy children. Vegetables are preferred as the first additional dish for a child. In the second half of life, when the child begins to be given meat products, sick children should receive them in very limited quantities. The correctness of the diet is assessed by the child’s well-being and laboratory test results.

Products such as beef, chicken, eggs, etc. are especially undesirable in a child’s diet. cow's milk, cottage cheese, cheese, peas, barley, rye, Wheat flour, rice.

Under the influence of diet therapy, seizures very quickly cease to bother the child. But speech disorders and mental retardation are not corrected in this way.

Treatment is also possible medications, but it does not eliminate the cause of the disease, affecting only certain of its manifestations.

The prognosis in most cases is favorable and is determined by timely diagnosis and treatment.

Hartnup disease

Opened in 1956. Associated with impaired absorption of the amino acid tryptophan in the intestine. It is quite widespread, but does not appear in all patients.

Signs of Hartnup's disease

First of all, attention is drawn to skin lesions that are similar to those caused by a deficiency of B vitamins. Allergic skin lesions to sunlight often occur. There are a wide variety of violations from nervous system. There is twitching eyeballs, trembling of the fingers when working with small objects, disturbances in the normal tension of the muscles of the arms and legs, movements in them, coordination of movements associated with damage to the cerebellum.

When making a diagnosis, we are guided by data laboratory research: biochemical analysis blood, urine.

Treatment of Hartnup's disease

Treatment consists mainly of therapeutic diet. The amount of protein-containing foods in a child's diet should be limited. Increase the amount of fruit consumed. From medicinal methods administration is prescribed vitamin preparations various groups. It is necessary to protect the child's skin from direct sunlight.

Since nitrogen metabolism mainly combines the exchange of proteins, the structural units of which are amino acids. Disturbances in this metabolism are called proteinopathies, i.e. diseases of “specific proteins”. For such disorders, Pauling introduced the concept of “molecular diseases” or “molecular pathologies” in 1049.

Proteinopathies are:

1. Enzymatic (enzymopathies or enzymopathies);

2. Non-enzymatic (associated with defects in non-enzymatic proteins that perform other functions: transport, immunological, receptor);

3. Mixed, when the protein combines catalytic and some other function.

The most important sign proteinopathies - blocking of the chain and transformation of substances caused by enzyme deficiency. For example, the conversion of substrates A, B, C is catalyzed by enzymes E1, E2, E3

Enzymepathies amino acid metabolism

Basic metabolic transformations of phenylalanine and tyrosine.

The numbers in the circles are areas of blocking reactions in phenylketonuria (Block 1), tyrosinosis (Block 2), albinism (Block 3) and alkaptonuria (Block 4).

E block 1 – phenylalanyl hydroxylase

E block 2 – tyrosinase

E block 3 – n-hydroxyphenylpyruvate oxidase

E block 4 – homogentisate oxidase

Phenylalanyl– essential AK, in case of disruption of its exchange, as well as in case of disturbance of exchange tyrosine, the most common 4 types of molecular diseases are:

Enzyme disorders

Phenylketonuria(phenylpyruvic oligophrenia) associated with defect E phenylalanine hydroxylase(Block 1), which catalyzes the conversion of phenylalanine to tyrosine. At the same time, the content of phenylalanyl and its breakdown products – phenylpyruvate, phenyllactate and phenylacetate – increases in the blood and urine.

Biochemical diagnostic sign – increased levels of phenylalanine in the blood and phenylpyruvate in the urine.

Phenylpyruvate is toxic substance for brain cells on the one hand, and on the other hand, when accumulated, it affects the metabolism of substances important for the central nervous system (for example, it reduces the content of serotonin).

With phenylketonuria, the content of phenylalanyl in the blood can reach 600 mg/l (normally 15 mg/l), in cerebrospinal fluid– 80 mg/l (normal 1.5 mg/l). Characteristics illness - a sharp slowdown in the child’s mental development, convulsions. The development of the disease can be prevented by significantly reducing dietary phenylalanine intake from birth.

Albinism– congenital absence of pigments in the skin, hair and retina. The metabolic defect is associated with the loss of the ability of melanocytes to synthesize tyrosinase– an enzyme that catalyzes the oxidation of tyrosine into dioxyphenylalanine (DOPA) and dioxyphenylalanine quinone (DOPAC), which are precursors of melanin.

Characteristic signs– weak skin pigmentation, blond hair, reddish color of the iris (due to translucent capillaries). This does not cause any serious problems; you just have to avoid direct sunlight.

Tyrosinemia– block 3. With deficiency of E parahydroxyphenylpyruvate hydroxyoxidase homogentisic acid is not formed, i.e. the content of tyrosine and n-hydroxyphenyl increases pyruvic acid in blood and urine. Sick children experience developmental delays.

Alkaptonuria– block 4, defect E homogentisite oxidase. It is characterized by excretion in the urine of large quantities (up to 0.5 g/day) of homogentisic acid, the oxidation of which by atmospheric oxygen gives the urine dark color(as a result of polymerization of homogentisic acid with the formation of black pigment - alkaptone). In advanced cases, ochronosis develops, deposition of alkaptone pigment in tissues, tendons, cartilage, joints and darkening of the nose, ears and sclera are observed. With significant deposition of alkapton in the joints, their mobility is impaired.

Hartnup disease The metabolic defect is associated with a congenital malabsorption of tryptophan in the intestine and reabsorption of tryptophan and tryptophan and its metabolic products in the renal tubules.

The main manifestation of the disease, in addition to pellagra-like skin lesions, mental disorders and ataxia (impaired coordination of movement), serves as hyperaminoaciduria (increased concentration of indolyl acetate and indican (FAPS + indole) in the urine). By chemical composition indolyl derivatives in the urine and blood, one can judge the nature of the disease (carcinoid tumor, phenylketonuria, etc.) and the mechanism of tryptophan metabolism disorder, which is important for the diagnosis correct diagnosis and conducting adequate treatment

Non-enzyme disorders

Aminoaciduria – a defect in the proteins of one of the AA transport systems in the kidneys, where their reabsorption occurs, is accompanied by a loss of AA in the urine 3-5 times more than normal. Distinguish increased And reduced excretion of amino acids.

Hyperaminoaciduria divided by renal related to acquired or birth defects reabsorption of amino acids in the kidneys, and extrarenal, caused by an increase in the concentration of all or individual amino acids in the blood.

Reabsorption of amino acids (reabsorption) in the kidneys occurs against the concentration gradient. At chronic nephritis More lysine, arginine, proline and citrulline are excreted in the urine, although their blood levels may remain within normal limits. With nephrosis, more ethanolamine, taurine and β are almost always released -aminobutyric acid, and this hyperaminoaciduria is considered an unfavorable prognostic sign. This pathology occurs in children early age in poor families, when they eat food poor in protein (bananas, rice).

Hereditary defects are more common absorption of AA in the kidneys.

The main metabolic defect is associated with a congenital disorder of reabsorption of almost all amino acids (with the exception of cyclic ones) in the renal tubules; the consequence of this is an increase in amino acid excretion by 5–10 times, cystine and cysteine ​​by 20–30 times, and selective deposition of cystine in reticular cells bone marrow, spleen, liver and cornea cells.

Cystinuria- a fairly common hereditary disease. The metabolic defect is expressed in the excretion in urine of 50 times the normal amount of 4 amino acids: cystine, lysine, arginine and ornithine.

The level of cystine in the blood is usually not higher than normal. People suffering from cystinuria are quite healthy, except for the tendency to form stones in the body. This congenital metabolic abnormality is caused by complete blocking of cystine reabsorption and partial violation absorption of three other amino acids in the kidneys; No disturbances in the intermediate metabolism of these amino acids were detected.

Hepatocerebral dystrophy (Wilson's disease). In addition to generalized (general) hyperaminoaciduria, there is a decrease in the concentration of copper-containing protein ceruloplasmin in the blood serum and copper deposition in the brain, liver, and kidneys. Genetic defect associated with impaired synthesis ceruloplasmin. It is possible to form complexes of copper with amino acids that are not absorbed in the tubules. Similar hyperaminoaciduria is observed with galactosemia, Lowe's syndrome and others hereditary diseases. Decreased amino acid excretion has been described in kwashiorkore.

The intermediate metabolism of amino acids consists of the reactions of deamination, transamination and decarboxylation.

Rice. 21. Metabolism of amino acids.

Deamination. This is the stage of interstitial amino acid metabolism, during which the formation of keto acids and ammonia occurs. Deamination is carried out by the enzyme amine oxidase, the coenzyme of which is FAD or NAD.

L-glutamate →N.H. 3 + α -ketoglutarate

Deamination is a universal process in the formation of amino acids, when amino acids not used for protein synthesis lose amino groups and are converted into nitrogen-free products. Ammonia is formed from the amino group, and keto acids are formed from the nitrogen-free part.

Thanks to education α -ketoglutarate deamination ensures the functioning of the Krebs cycle, and thanks to the formation ammonium ions in the renal tubules – participates in the regulation of the acid-base state (ammoniogenesis).

Causes and consequences of deamination deficiency.

This process is weakened with liver damage, with hypoxia, with vitamin deficiencies C, PP and B2.

Violation of deamination leads to a weakening of urea formation and an increase in amino acids in the blood ( aminoacidemia), which is accompanied aminoaciduria.

Also, the consequences of a decrease in deamination are: a decrease in protein synthesis due to insufficiency of adjacent transamination reactions, suppression of the activity of the Krebs cycle, energy production, acidosis, hyperammonemia.

Causes and consequences of excess deamination.

The reasons for the increase in deamination may be: fasting, when the body's energy needs are satisfied by protein.

The consequences of increased deamination are an increase in the formation of α-ketoglutarate, leading to an increase in energy production and the formation of keto acids, a decrease in protein synthesis, an increase in ammonia synthesis and an increase in urea formation.

Transamination(transamination) is a reversible transfer of an amino group from an amino acid to a keto acid without the intermediate formation of ammonia to form a new keto acid (KA) and a new non-essential amino acid. Amino acids are amino group donors, and keto acids are acceptors.

Transamination occurs in the presence of a coenzyme, the role of which is played by pyridoxal phosphate (vitamin B 6).

Transamination supplies keto acids (oxaloacetic acid) to the Krebs cycle, thereby supporting energy metabolism, and pyruvic acid to ensure gluconeogenesis and the synthesis of non-essential amino acids.

When the amino group is transferred to α-ketoglutarate, the collector substance L-glutamate is formed:

A-ta +α -ketoglutarate ↔ KK (PC, SHUK) +L-glutamate

L-glutamate is used in the synthesis of urea.

Reasons for decreased transamination:

hypovitaminosis B6 due to insufficient vitamin content in food, with a high need during pregnancy, with a violation of its absorption and phosphorylation during treatment with ftivazide, with suppression of the intestinal microflora that partially synthesizes the vitamin, under the influence of long-term use of sulfonamide drugs.

restriction of protein synthesis (with fasting and severe liver diseases, with insufficiency of the adrenal cortex and thyroid gland).

Consequences of reducing transamination:

reduction in the synthesis of non-essential amino acids (alanine from pyruvic acid, asparagine from oxaloacetic acid);

hypoglycemia due to decreased gluconeogenesis;

aminoacidemia due to decreased urea synthesis;

acidosis in the muscles due to an increase in pyruvic acid (PA) in the muscles (due to impaired transport to the liver)

PC+L-glutamate →α -Alanine +α -ketoglutarate

formation of toxic substances due to activation of decarboxylation.

During the transamination process, nicotinic acid is formed from tryptophan. The absence of phosphopyridoxal leads to disruption of the synthesis of nicotinic acid, resulting in the development of pellagra.

For a number of reasons (excess of keto acids (PC, α-ketoglutarate, increase in glucocorticoids), an increase in transamination is noted.

Consequences of increased transamination:

reduction in the content of essential amino acids

decreased protein synthesis,

increased urea synthesis and hyperazotemia.

If necrosis occurs in individual organs (pancreatitis, hepatitis, myocardial or pulmonary infarction), then due to cell destruction, tissue transaminases enter the blood and an increase in activity in the blood is one of the diagnostic tests. Increased levels of aspartate aminotransferase (AST) are characteristic of heart disease and alanine aminotransferase (ALT) - characteristic of liver disease.

Decarboxylation. This is the process of removing carboxyl groups from amino acids in the form of CO 2 .

Amino acid → Amines (biogenic) + CO 2

Primary amines are formed by decarboxylation of amino acids. All amino acids enter into this reaction. The decarboxylation process is carried out by specific decarboxylases, the coenzyme of which is phosphopyridoxal (vitamin B 6).

Only some amino acids undergo decarboxylation to form biogenic amines and carbon dioxide.

histidine → histamine

The histamine content increases with allergic diseases (bronchial asthma, Quincke's edema, etc.), with burns, tumor disintegration, with shocks (anaphylactic, traumatic and blood transfusion), with poisonous insect bites, with nervous excitement, oxygen starvation. Excess histamine increases vascular permeability, causes dilatation, disrupts microcirculation, and causes spasm of smooth muscles.

tryptophan → tryptamine → serotonin

Serotonin is produced in the mitochondria of chromaffin cells in the intestine. It is destroyed mainly in the lungs by the enzyme amine oxidase. Serotonin increases smooth muscle tone, vascular tone and resistance, is a mediator of nerve impulses in the central nervous system, and reduces aggressiveness. The content of serotonin in the blood increases with intestinal carcinoid, with exacerbation of chronic pancreatitis, and immobilization stress in rats.

glutamic acid → gamma-aminobutyric acid (GABA)

Gamma-aminobutyric acid (GABA) inhibits synaptic transmission of the superficial layers of the cerebral cortex.

tyrosine → tyramine (false transmitter)

DOPA → dopamine

cystine → taurine

The reasons for the increase in the content of biogenic amines may be not only an increase in the decarboxylation of the corresponding amino acids, but also the inhibition of the oxidative breakdown of amines and the disruption of their connection with proteins. For example, under hypoxic conditions, ischemia, tissue destruction (trauma, radiation, etc.), oxidative processes are weakened, which reduces the conversion of amino acids along the path of their usual breakdown and enhances decarboxylation.

The appearance of large amounts of biogenic amines in tissues (especially histamine and serotonin) can cause significant disturbances in local circulation, increased vascular permeability and damage to the nervous system.

A decrease in decarboxylation activity is observed during hypoxia and vitamin B6 deficiency.

Hypoxia and acidosis reduce the production of GABA, a deficiency of which causes seizures; insufficient formation of the neurotransmitter serotonin causes emotional disturbances.

Since the human body has no reserve sources of protein, then protein metabolism solely dependent on dietary proteins. A lack of proteins in the diet or a deficiency of certain amino acids leads to incomplete absorption of others and disruption of protein metabolism in general. That is why daily consumption proteins are regulated by the Ministry of Health

Rice. 12.16.

opinion of the Russian Federation and must comply physiological need, which takes into account a person’s age, weight, gender and level of physical activity.

To assess the biological usefulness of food proteins, there are different methods. Biological methods include studies of protein composition using microorganisms and animals.

Microbiological studies give good results, but they cannot be completely identified with the absorption of protein in the human body, since this method The processes of protein digestion in the gastrointestinal canal are not taken into account at all.

Conducting clinical trials with animals is enough reliable way assessing the biological usefulness of proteins, but very labor-intensive and economically expensive.

The most widely used method in practice is the calculation method for assessing the biological usefulness of proteins - determination of amino acid score. This method compares the content of essential amino acids in the studied and ideal protein according to the formula

where AK speed is amino acid speed, %; | AK mg) | - mass of amino acid in the protein under study, g; [AK eb] - mass of amino acid in the reference protein, g.

The method was proposed back in 1946 by H. Mitchell and R. Block. Currently, according to the decision of FAO and WHO, the ideal or reference protein in terms of amino acid composition considered the white of an egg.

The amino acid with the lowest rate is called limiting.

To assess protein metabolism in the body, a calculation is used nitrogen balance(AB). This is easily explained, since the bulk of nitrogen in the body is associated with proteins. For calculations you need to know:

• the amount of nitrogen supplied with products (N n) is on average 16% of the total mass of protein in products;
• the amount of nitrogen excreted from the body with final products(N K), - you can approximately take the urea content in urine, since urea nitrogen accounts for up to 95% of the total urine nitrogen.

As a result, three options are possible: positive nitrogen balance, negative nitrogen balance, or nitrogen balance.

Positive nitrogen balance Normally observed during the period of growth and development, when new tissues are formed, for example during pregnancy. However, a positive nitrogen balance may result from pathological disorders- liver disease, kidney disease or taking anabolic hormonal drugs.

Negative nitrogen balance can also be called either pathological changes in the body, or a deficiency of proteins or even essential amino acids in foods. For example, protein intake should be increased during lactation. It is believed that the synthesis of 1 g of milk protein requires 2 g of food proteins. In this regard, the protein content in a nursing woman’s diet should be increased twice as much as the amount of protein excreted in milk per day 1 .

Nitrogen balance - the norm for adult healthy organisms when the required amount of complete proteins is supplied with food.

Monitoring carried out by specialists from the Institute of Nutrition of the Russian Academy of Medical Sciences among the population of Russia and WHO data indicate an insufficient content of biologically complete proteins in the diet of modern people.

Table 12.7

Protein and amino acid metabolism disorders

violations		Result
Protein starvation	Deficiency of digestible protein and essential amino acids in the diet. Diseases of the alimentary canal, liver, pancreas	General weakness, slower growth, decreased productivity of V animals. Hypoproteinemia. Negative nitrogen balance. Decline osmotic pressure blood, impaired water-mineral metabolism, “hungry” edema
Metabolism of complex proteins	Chromoproteins - various lesions liver	Hyperbilirubinemia, urine becomes dark. Porphinuria, urine turns red
	Pucleoproteins - disorders of purine base metabolism (gout)	Sediments uric acid and its salts in cartilage, tendons and other organs. Joint deformity and pain

1 Karimova Sh. F., Sultanov R. G., Ziyamutdinova Z. K. Decree. Op.

Disorders of protein metabolism also include disturbances in the metabolism of chromo- and nucleoproteins (Table 12.7), although the listed examples reflect changes observed during the breakdown of the non-protein part of these compounds.

If we take into account not the medical, but the nutritional aspects of such pathologies, then some of them can be significantly reduced by changing the diet. For example, traditional recommendations for gout are to reduce total calories and purines, which accompany meat broths, offal (liver, kidneys), alcohol. Metabolism disorders of individual amino acids (see paragraph 12.2) caused by hereditary reasons, can also be adjusted thanks to the right choice products, for example, for phenylketonuria.

(Yu.I. Barashnev, Yu.E. Veltishchev, 1978)

1. Hereditary disorders metabolism of amino acids, accompanied by an increase in their concentration in the blood and urine: phenylketonuria, histidinemia, tryptophanuria, maple syrup disease, ornithinemia, citrullinemia, etc. Inheritance is mainly autosomal recessive. The development of diseases is based on a violation of the synthesis or structure of certain enzymes.

2. Hereditary disorders of amino acid metabolism, accompanied by an increase in their excretion in the urine without changing the level in the blood: homocystinuria, hypophosphatasia, arginosuccinate aciduria, etc. With these enzymopathies, the reverse suction in the kidneys, which leads to an increase in their content in the urine.

3. Hereditary disorders of amino acid transport systems: cystinuria, tryptophanuria, Hartnep's disease, etc. This group includes enzymopathies, the development of which is caused by a decrease in the reabsorption of amino acids in the kidneys and intestines.

4. Secondary hyperaminociduria: Fanconi syndrome, fructosemia, galactosemia, Wilson-Konovalov disease, etc. In these conditions, secondary generalized hyperaminoaciduria occurs as a result of secondary tubular disorders.

Phenylketonuria (PKU)

First described in 1934 by Folling under the name “phenylpyruvic imbecility.” The type of inheritance is autosomal recessive. The incidence of the disease is 1:10,000-1:20,000 newborns. Prenatal diagnosis is possible using genetic probes and chorionic villus sampling.

Towards the development of classical clinical picture PKU is caused by deficiency of phenylalanine hydroxylase and deficiency of dihydropterin reductase, the 2nd enzyme that ensures the hydroxylation of phenylalanine. Their deficiency leads to the accumulation of phenylalanine (PA) in body fluids (Scheme 1). As is known, FA refers to essential amino acids. When supplied with food and not used for protein synthesis, it breaks down along the tyrosine pathway. In PKU, there is a restriction in the conversion of FA to tyrosine and, accordingly, an acceleration of its conversion into phenylpyruvic acid and other ketonic acids.

Scheme 1. Variants of phenylalanine metabolism disorders.

The existence of various clinical and biochemical variants of PKU is explained by the fact that phenylalanine hydroxylase is part of a multienzyme system.

The following forms of PKU are distinguished:

1. Classic

2. Hidden.

3. Atypical.

The development of atypical and latent forms of PKU is associated with deficiency of phenylalanine transaminase, tyrosine transaminase and parahydroxyphenylpyruvic acid oxidase. Atypical PKU is usually not accompanied by damage to the nervous system as a result of the late development of an enzymatic defect.

Women with phenylketonuria may give birth to children with microcephaly, mental retardation, and developmental disorders of the urinary system, so it is necessary to prescribe diet therapy during pregnancy.

Clinical symptoms in patients with PKU

At birth, a child with phenylketonuria appears healthy. The disease in these children manifests itself in the first year of life.

1. Intellectual defect. An untreated child loses about 50 IQ points by the end of the 1st year of life. In patients, there is no relationship between the level of physical activity and the degree of intellectual defect.

2. Convulsive syndrome(4 50%), eczema, hypopigmentation.

3. Impaired movement coordination.

4. Delayed development of static and motor functions.

5. Damage to the pyramidal tracts and striopallidal system. Clinical manifestations classical PKU is rare in countries where the program operates neonatal screening for this disease.

Children with phenylketonuria have increased urinary levels of FA metabolites. Increase in physiological fluids content of FA and under-oxidized products of its metabolism leads to damage to the nervous system. A certain role in these disorders belongs to an imbalance of amino acids (deficiency of tyrosine, which normally is actively involved in the construction of the protein component of myelin). Demyelination is a characteristic pathological sign of phenylketonuria. Violation of the ratio of amino acids in

blood leads to disruption of the level of free amino acids in the brain, which causes dementia, hyperkinesis and other neurological symptoms.

Pyramidal symptoms are caused by impaired myelination processes. The selective nature of the damage to the nervous system is explained by the peculiarities of myelination; the phylogenetically youngest parts that perform complex and differentiated functions are affected. Insufficient formation of melanin from tyrosine is associated with blue eye color and fair skin. The smell of "mold" ("mouse", "wolf") is explained by the presence of phenylacetic acid in the urine. Skin manifestations(exudative diathesis, eczema) are associated with the release of abnormal metabolites. Insufficient formation of adrenergic hormones from tyrosine leads to arterial hypotension.

It should be noted that with PKU in pathological process the liver is involved, but the nature of the morphological disorders is not specific: signs of tissue hypoxia, disturbances of oxidative and protein synthesizing functions, and lipid overload are revealed. Along with this, compensatory and adaptive changes are observed: high glycogen content, mitochondrial hyperplasia. Generalized hyperaminoacidemia in PKU can be explained secondary violation amino acid metabolism due to damage to hepatocytes, because many enzymes involved in amino acid metabolism are localized in the liver.

In untreated patients with classical PKU, there is a significant decrease in the concentration of catecholamines, serotonin and their derivatives in the urine, blood, and cerebrospinal fluid. Therefore in complex treatment PKU requires promediator correction, since a partial intellectual defect may be associated with neurotransmitter disorders.

Criteria for diagnosing the classic form of phenylketonuria:

1. Plasma FA level is above 240 mmol/l.

2. Secondary tyrosine deficiency.

3. Increased level in urine of FA metabolites.

4. Reduced tolerance to ingested PA.

Methods for diagnosing phenylketonuria:

1. Felling's test with FeCl 3 - at positive analysis A blue-green color appears in the urine.

2. Detection of excess phenylalanine in the blood is possible using bacterial express test Goldfarb or Guthrie test (since during the first days of life, phenylpyruvic acid may be absent in the urine).

In case of PKU, treatment is carried out with a diet with a limited content of PA (mainly vegetable dishes, honey, and fruits are prescribed). Products such as milk, dairy products, eggs, fish should be completely excluded during the stay of patients with PKU on acute diet. Appointed special drugs(cymogran, lofenalac) and vitamins.

The optimal time for examination of newborns is 6-14 days of life, the start of therapy is no later than 21 days of life. It must be remembered that conducting the study on the first day does not exclude false-positive or false-negative results (repeated studies are carried out up to 21 days of life). The effectiveness of treatment is assessed by the patient’s intellectual level of development. It should be noted that treatment started after a year does not completely normalize intelligence (this may be due to the development of irreversible changes in the brain).