Hereditary metabolic diseases

Among hereditary human diseases one of the most significant places is occupied by hereditary metabolic diseases. This is a fairly large group of diseases, which includes about 700 different diseases. For 200 of them, the immediate cause, i.e., a genetic mutation, is located in the human chromosome. Most of the metabolic disorders is due to a congenital insufficiency of a certain enzyme, the cause of which is the genetic mutation. When the enzyme is deficient, it either does not form in the human body at all, or is formed, but differs from normal with low activity, which leads to metabolic disturbances. The enzyme is a substance without which various chemical reactions that form the basis of metabolism can not flow. The loss of this function of the enzyme creates a block in the appropriate chemical reaction. As a result, there is an accumulation of metabolites immediately preceding the block and a deficiency in the final reaction products;the metabolic block can also lead to disruption of the transport of individual compounds.

Chemicals accumulated before the block are quite often toxic. So, if a certain enzyme is deficient, not only amino acid phenylalanine but also phenylpyruvic acid accumulates in the blood and tissues, which has a toxic effect on the child's brain in such a disease as phenylketonuria. Hereditary disorders of urea synthesis can lead to accumulation in the blood and tissues of ammonia, which is also accompanied by a toxic lesion of the central nervous system.

Many diseases are caused by a deficiency in the end products of metabolism stopped as a result of a certain block. An example is the hereditary diseases of the synthesis of hormones( adrenogenital syndrome, hypothyroidism, hypoparathyroidism).

A number of hereditary metabolic diseases is caused by a deficiency in the body of vitamins. In some cases, the absence or decrease in the activity of the corresponding enzyme can be partially restored by the administration of elevated doses of the vitamin. Such metabolic disorders are called congenital vitamin-dependent. When, as a result of a genetic mutation, the formation of an enzyme is completely broken or an enzyme with a broken structure is formed, devoid of its activity, then the administration of increased doses of the vitamin does not give any effect. Such violations of deception of substances are called vitamin-resistant( resistant to the introduction of vitamins) of congenital disorders.

A number of hereditary metabolic diseases may be caused by micronutrient deficiencies. More than 180 enzymes of the human body are metalloproteins, that is, they have molecules or metal ions in their composition. Such metals are, for example, copper, zinc, manganese, magnesium, molybdenum, cobalt, selenium. The micronutrient deficiency may be due to the characteristics of the environment in which a person lives, although in most cases it is more often associated with impaired absorption or transport of metals in the body.

Most of all hereditary metabolic diseases are inherited by recessive( autosomal or X-linked) type. Dominant inheritance is extremely rare.

There are various classifications of NBO - by type of inheritance, by the nature of metabolic disorders and others, but none of them is exhaustive and does not fully reflect the entire complex complex of this pathology.

The recognition of hereditary metabolic diseases by emerging symptoms seems rather difficult. Change in enzyme activity causes various metabolic disorders, which leads to a wide variety of symptoms. In some cases, the signs of a person emerging from a person can be associated with a very serious pathology and lead to death in the neonatal period, some lead to persistent mental retardation and disability. Sometimes, metabolic disorders are accompanied by less pronounced symptoms or occur with complete absence.

Despite the variety of symptoms of hereditary metabolic diseases, it is possible to distinguish common signs on the basis of which it is possible to draw conclusions about the presence of a disorder in a child. These signs include: delay in mental development, disorders of the nervous system, repeated convulsions and coma, a specific smell of urine and body( sweaty feet, cat urine, mouse smell, maple syrup smell), muscle damage, skeletal abnormalities, hair changes andskin, cataracts, enlarged liver and spleen, digestive disorders, unexplained deaths of siblings. Many hereditary diseases of the exchange are manifested already in the period of neonatal, but are rarely recognized. This is due to the fact that deviations in the health of the child are often considered by doctors as the consequences of lack of oxygen during pregnancy and intracranial birth trauma. A distinctive feature of hereditary diseases in newborns is the presence of an asymptomatic period, which can last 2-3 days after birth. Children are born apparently healthy, and their condition worsens suddenly.

Various metabolic diseases rarely have characteristic features, but for symptoms that arise in humans they can be combined into two main groups: toxic type and hypoenergetic type. The defeat of the brain of a toxic type is associated with the accumulation of toxic metabolic products in the body. These can be organic acids, ammonia and many other substances. Common manifestations of toxic lesions are: breast failure, vomiting, lethargy and coma, convulsions, respiratory arrest, muscle and kidney failure, hypertension and muscle clone, loss of a large amount of fluid. The defeat of the brain of the hypoenergetic type is characterized either by the depletion of energy reserves, or by the impossibility of using them by the body. This type of lesion is manifested by the same signs( vomiting, lethargy, coma), but with a marked decrease in muscle tone, a decrease or total absence of reflexes, heart damage, vascular insufficiency, fainting and even sudden death.

Early diagnosis of hereditary metabolic diseases before the appearance of characteristic symptoms, the presence of which already speaks of the irreversibility of processes in the human body, is necessary primarily for the timely correction of metabolic disturbances, as well as to prevent possible menacing consequences. To this end, screening programs have become widespread in recent decades. They are used to identify in the population of certain types of hereditary metabolic diseases. Massively examine all newborn children, as well as individuals from special risk groups, for example children with various developmental disabilities. Screening programs include two stages. At the first stage, the suspected patients or carriers of individual hereditary metabolic diseases are identified, on the second stage, a more complete examination and definitive recognition of the disease is carried out. In modern programs of mass screening, methods of determining pathological products of metabolism in blood are used primarily.

There are a number of criteria for selecting individual metabolic diseases as a screening object:

1) the disease should be fairly common in a population with a frequency of at least 1: 100,000 newborns;

2) the disease without timely detection and treatment leads to severe health problems;

3) there are ways to treat the disease;

4) there are adequate diagnostic tests for detection;

5) the costs of implementing screening programs do not exceed the funds needed to service this category of patients.

In view of these criteria, it was recognized that mass screening is necessary to detect phenylketonuria, hypothyroidism, adrenogenital syndrome, galactosemia and other metabolic diseases.

Examination of individual risk groups, especially children lagging behind in psychomotor and physical development, is necessary to prevent the severe consequences of metabolic diseases. Timely detection of the disease contributes, in addition to preventing the disability of children;Effective genetic counseling of the families of the subject, which prevents the spread of the disease in the family and society.

Currently, the principles of treatment of hereditary metabolic diseases have been developed. They include the following items:

1) adherence to a specific diet for the purpose of excluding from the diet products containing substances that are not fully cleaved and subsequent transformations occurring in a healthy body. Thus, the accumulation of toxic substances is excluded;

2) the introduction of missing regulators of metabolism( hormones, vitamins B6, B12, etc.);

3) substitution of missing enzymes;

4) transplantation of organs and tissues( kidney, bone marrow, heart);

5) elimination or limitation of the influence of unfavorable environmental factors( elimination of sun exposure in diseases with increased or distorted skin sensitivity, withdrawal of drugs, aggravating metabolic disorders);

6) specific methods of treatment.

The medical treatment of mental retardation in hereditary metabolic diseases involves the use of stimulants of the central nervous system. They improve metabolic processes in the nervous tissue and play a major role in the development of psycho-speech and motor development in children. In complex treatment a big role is given to vitamins. When hereditary diseases of the endocrine system exchange, often appropriate hormones are used. When the formation of bone tissue is disturbed, the reception of hormonal preparations in combination with preparations of calcium, phosphorus, group B vitamins, citrates, antioxidants is highly effective.

In the prevention of hereditary diseases of metabolism, a special role belongs to prenatal diagnosis. The subjects of the study are either chorion cells at the 7-9 week of pregnancy, or amniotic fluid taken for a 16-17 week gestation study. Currently, prenatal diagnosis is possible with more than 60 different hereditary metabolic diseases.