Glycogenoses - a group of fairly rare hereditary diseases associated with the defects of various enzymes necessary for the synthesis and decomposition of glycogen. In this case, the accumulation of normal or "incorrect" glycogen in the organs and tissues of a person, which causes clinical manifestations of the disease. The primary accumulation of glycogen can occur in the liver, muscles, kidneys. In total, 12 forms of glycogenosis, the difference of which consists in the nature of enzyme deficiency, are described. The prognosis for each type of glycogenosis is different: some have a favorable course, and the patients live to old age, others - they end lethal even in childhood. Diseases are classified as incurable, specific therapy is currently not available. The main role in the treatment is given to dietotherapy with a high carbohydrate content. In this article we will talk about all known types of glycogenosis, their symptoms and treatment options.
- 1What is glycogen and what is it for?
2Types of glycogenases
- 2.1Glycogenosis of type 0 (aglycogenosis)
- 2.2Glycogenosis type I (Girke's disease)
- 2.3Glycogenosis type II (Pompe disease)
- 2.4Glycogenosis type III (Cory's disease, Forbes disease, limidextrinosis)
- 2.5Glycogenosis type IV (Andersen's disease, diffuse glycogenosis with cirrhosis of the liver, amylopectinosis)
- 2.6G type glycogenesis (Mc-Ardl's disease, myophosphorylase insufficiency)
- 2.7Glycogenosis of type VI (Gears disease, hepatophosphorylase deficiency)
- 2.8Glycogenosis of the VII type (TARUI disease, myophosphofructokinase insufficiency)
- 2.9Glycogenosis VIII type (Thomson's disease)
- 2.10Glycogenosis IX type (Hag's disease)
- 2.11Glycogenosis of type X
- 2.12Glycogenosis of the XI type (Fanconi-Bickel disease)
What is glycogen and what is it for?
Glycogen is a complex carbohydrate, which is synthesized by interconnecting glucose molecules, which comes with food. It is a strategic stock of glucose in cells. It is stored mainly in the liver and muscles with the feature that the glycogen from the liver during its splitting provides the whole human body with glucose, and glycogen from the muscles is only the muscles themselves. Glycogen in the liver can be 8% of its weight, and in muscles - only 1%. But at the same time, due to the fact that the total muscle mass in the body is much larger than the weight of the liver, the muscle reserve exceeds the hepatic capacity. A small amount of glycogen is contained in the kidneys.
As soon as a person embarks on some sort of activity (physical or mental), he needs the energy that he derives from the breakdown of glycogen and glucose. At first, glucose is contained in the blood, but when its reserves are exhausted (and there is no external input), glycogen is consumed. The consumed glycogen reserve is then replenished (when food arrives).
Thus, glycogen allows a person to be active at relatively large breaks in food, and not be "tied to a plate".
Stages of conversion of glucose into glycogen and its cleavage in the opposite direction are carried out with the help of various enzymes, and in the liver and muscles they are different. Violations of the activity of such enzymes lead to the development of glycogenoses.
Glikogenozy occur, on average, with a frequency of 1 case per 40-68 000 population. They are always hereditary, that is, they arise when, as a result of gene disorders, the quantity or the activity of one of the enzymes required for biochemical processes of creation and cleavage of glycogen. The type of inheritance, basically, is autosomal recessive (it is not connected with the sex, and for its emergence, a coincidence of pathological genes obtained from the father and from the mother is necessary). Of the 12 varieties of glycogenases known to date, 9 are hepatic forms, 2 - muscular, 1 - either muscular, or generalized (with the defeat of almost the entire body). Each of the glycogenoses has its own distinctive features.
Types of glycogenases
Glycogenosis of type 0 (aglycogenosis)
This type of glycogenesis occurs when a defect of the enzyme involved in the creation of glycogen from glucose, resulting in glycogen simply does not form in sufficient quantities. That is, there is a deficiency of glycogen, so this glycogenosis is under the zero number, as if apart from the others.
With aglycogenosis, once all the sugar in the blood is consumed, a hypoglycemic syndrome develops with a loss of consciousness right up to the coma. The disease manifests itself almost from the first days of life, especially if the mother does not have enough milk during breastfeeding. Large breaks between feedings, the night interval become the causes of the development of coma.
Coma develops as a result of the lack of sufficient energy supply to the brain. Very likely the death in early childhood. If they manage to survive, then the development of such children, both mental and physical, differs significantly from peers for the worse. The introduction of glucose intravenously removes such patients from the coma, however, hyperglycemia persists for a long time (since glycogen is not synthesized).
Glycogenosis type I (Girke's disease)
The source of this variety is the deficiency of glucose-6-phosphatase. The consequence is an excessive accumulation of glycogen in the liver and kidneys. In the blood there is a low glucose content (hypoglycemia). There is a kind of paradox: glycogen excess, but there is nothing to split it, so there is a deficiency of glucose. Patients require very frequent meals, so that the concentration of glucose in the blood is sufficient to meet energy needs.
The disease manifests itself in the first years of life. Such children have no appetite, frequent vomiting occurs. There are problems with breathing due to metabolic disorders: shortness of breath, cough. Hypoglycemia can lead to the development of coma with convulsions. Often the temperature rises without infectious causes.
The deposition of glycogen in the liver and kidneys leads to an increase in these organs with a violation of their function. Because of liver damage, hemorrhagic syndrome develops (a tendency to spontaneous bleeding), a violation of the filtration function of the kidneys leads to the accumulation of uric acid. If the fatal outcome does not overtake patients at an early age, they subsequently lag behind in physical development, have a disproportionate body (a large head with a "puppet" facial expression). Mental development does not suffer. Characterized by hypotension and muscle hypotrophy. Sexual maturation occurs much later than in peers. In some patients there is a decrease in the number of neutrophils in the blood. Secondary bacterial infections are often associated. Patients who managed to survive and grow up, overtake gouty nephropathy and liver adenomas. Renal damage causes loss of protein in the urine and increases blood pressure. Kidney failure may occur. Liver adenomas can degenerate into cancer.
Glycogenosis type II (Pompe disease)
This variety can be represented in two forms: generalized (a deficiency of the enzyme is observed in the liver, kidneys, muscles) and muscle (the enzyme deficiency only in the muscles).
The generalized form makes itself felt in the first six months of life. It is associated with a deficiency of α-glucosidase. Poor appetite, anxiety, lethargy, low muscle tone, developmental delay, respiratory disorders become the first symptoms. Gradually, the heart, liver, kidneys, spleen increase in size. On the part of the respiratory system, frequent bronchitis and pneumonia develop. Heart failure develops. The defeat of the nervous system manifests itself as paralysis, a violation of swallowing. The prognosis for life in generalized form is unfavorable.
The muscular form has a more favorable course. It is the result of a deficiency of acidic α-, -glucosidase only in the muscles. Declares itself later: about 15-25 years. The main manifestation of the muscular form is weakness and decreased muscle tone. In addition to muscle problems, there are violations of posture (scoliotic deformation of the thoracic spine), the phenomenon of minor heart failure. Patients with this form of the disease survive to old age.
Glycogenosis type III (Cory's disease, Forbes disease, limidextrinosis)
This is the most common glycogenosis. Its cause is the deficiency of amylo-, -glucosidase, resulting in the synthesis of abnormal glycogen. Wrong glycogen is deposited in the liver, heart and muscles. Initial signs of the disease are detected even in infants. Such children often have vomiting, a delay in physical development, a "puppet" face. Hypoglycemia can lead to loss of consciousness. Muscle tone is reduced, along with a thickening of muscles associated with the accumulation of glycogen. For the same reason, the heart muscle thickens (myocardial hypertrophy), which causes cardiac conduction and heart rhythm to be disturbed.
Sometimes after the period of puberty, the disease proceeds less aggressively. At the same time, liver disorders recede into the background, and muscle weakness and muscle thinning (mainly gastrocnemius) becomes the dominant symptomatology.
Glycogenosis type IV (Andersen's disease, diffuse glycogenosis with cirrhosis of the liver, amylopectinosis)
It is the result of a deficiency of amylo- (, -, ) -transglucosidase. This leads to the formation of abnormal glycogen. This kind of glycogenosis can be inherited sex-linked, and not only autosomal. From the first days of life begins the deposition of abnormal glycogen in the liver. This quickly leads to a disruption in the activity of the liver cells, stasis of bile, the development of hepatitis, and then liver cirrhosis. Jaundice, increased bleeding, increased abdominal size with accumulation of fluid in the abdominal cavity (ascites), skin itching, intoxication of the body - all these are consequences of developed cirrhosis of the liver. Generalized muscular hypotrophy and severe cardiomyopathy develop. Bacterial infections often join. The fatal outcome comes in 3-5 years of life.
G type glycogenesis (Mc-Ardl's disease, myophosphorylase insufficiency)
This is exclusively muscle glycogenosis, because the underlying cause is a flaw in an enzyme such as muscle phosphorylase. In muscle tissue, unsplit glycogen is deposited, which causes muscles to thicken and thicken, but become very weak and quickly fatigued. There are painful muscle spasms with physical activity, which can be accompanied by increased sweating and pallor of the skin, tachycardia. In the urine, muscle protein can be released. All these manifestations occur before adolescence and gradually increase. Perhaps the formation of contractures of large joints. In comparison with other types of glycogenosis, type V glycogenosis is a benign disease.
Glycogenosis of type VI (Gears disease, hepatophosphorylase deficiency)
This glycogenase is based on problems with liver phosphorylase. As a result, glycogen accumulates in the liver. Already in infants there is an increase in the size of the liver, there is a lag in the development of the child, the children gain less weight. Together with other metabolic disorders in the blood, an increased fat content is detected. An increased content of glycogen in red blood cells (erythrocytes) is noted.
Glycogenosis of the VII type (TARUI disease, myophosphofructokinase insufficiency)
The disease is associated with a deficiency of myofosfofructokinase muscles, because of which they cause the deposition of glycogen. According to its clinical signs, glycogenesis of type VII practically does not differ from type V glycogenesis and also has a relatively benign course.
Glycogenosis VIII type (Thomson's disease)
This glycogenosis does not know the exact genetic cause, and the flaw of the enzyme is found in the liver and brain. In the first place there are disorders in the nervous system. Characteristic is nystagmus (involuntary trembling movements of the eyeballs), which is called "dancing eyes "in this case, discoordination of muscle contractions, which is manifested by imprecision of movements. Gradually develop a violation of muscle tone, paresis, convulsive twitching. Neurological disorders are steadily progressing. The liver increases in size, the manifestations of liver failure increase. Such patients have no prospects to live to middle age, the disease ends in death in childhood.
Glycogenosis IX type (Hag's disease)
This is a kind of glycogenase transmitted with a sex chromosome. The source is a deficiency of the enzyme in the liver. Accumulation of glycogen leads to hepatic insufficiency.
Glycogenosis of type X
This species is described only once in the whole world. The inheritance type could not be established. The disease was accompanied by an increase in the liver, accompanied by pain and muscle strain when they were involved in the work.
Glycogenosis of the XI type (Fanconi-Bickel disease)
Glycogenosis with an unidentified transfer mechanism. Enzyme defects are found in the liver and kidneys. This type of glycogenesis is characterized by an increase in the size and compaction of the liver, a lag in growth. The difference from other varieties of glycogenoses is a decrease in the amount of phosphates in the blood and the development of rickets in connection with this. After reaching puberty, there is a tendency to some improvement in the state: the liver decreases in size, the phosphorus content is normalized, the children begin to grow.
Glycogenoses, like almost all genetic diseases, are an incurable pathology. All measures of medical care are, in essence, symptomatic. Nevertheless, since a number of glycogenoses have a favorable prognosis for life under a number of conditions (in particular type II muscular form, III, V, VI, VII, IX, XI type), the therapeutic measures help to reduce a number of symptoms and improve the patient's health.
The basis of treatment for glycogenoses is dietotherapy, which allows to avoid hypoglycemia and minor metabolic disorders in the body. The essence of the diet is to study the glycemic profile of the patient and the selection of such a mode of food intake, which will avoid the progression biochemical disorders (violations of the metabolism of fats, lactic acid) and will provide a sufficient level of glucose in the blood. Frequent, including night, feeding in young children helps to avoid hypoglycemia. Usually, food is prescribed that contains many proteins and carbohydrates, and fats are limited. The percentage ratio is approximately the following: carbohydrates - 70%, proteins - 10%, fats - 20%.
In order not to have to feed the child several times a night, raw corn starch (assigned to children over 1 year old), which is diluted with water in a ratio of 1: 2, can be used. Begin the introduction with a dose of 0.25 mg / kg, then gradually increase it so that the injected dose of starch is enough to provide the body with glucose for 6-8 hours, that is, overnight. Thus, the intake of starch at night allows you to abandon night feeding, which provides children with a full sleep without interruption.
In those cases when young children suffer from frequent attacks of hypoglycemia, and affect it only by observing the diet fails, an additional injection of pure glucose or a mixture enriched with maltodextrin is prescribed.
With type I glycogenesis, it is required to significantly limit products containing galactose and fructose (milk, most fruits). With type III glycogenosis, there are no such restrictions. With type VII, the intake of sucrose must be limited.
In a number of cases (especially when other, intercurrent diseases occur in such children), one enteral nutrition is not enough, as the body's need for energy rises. Then they resort to feeding through a nasogastric tube and intravenous infusions in a hospital.
Those types of glycogenoses, in which the defects of enzymes are localized only in the muscles, require the intake of fructose inside 50-100 g per day, a complex of vitamins, adenosine triphosphate.
Of the drugs for type I glycogenesis use calcium preparations, vitamin D and B1, allopurinol (to prevent gout and urate deposits in the kidneys), nicotinic acid (to reduce the risk of calculous cholecystitis and prevent pancreatitis). If the protein starts to be excreted, then angiotensin-converting enzyme inhibitors (Lysinopril, Enalapril and others) are prescribed.
For glycogenase type II, specific enzyme therapy (substitution therapy) has been developed. The drug Myosim is administered at 20 mg / kg every two weeks. Myozyme is an artificial human enzyme α-glucosidase, created with the help of genetic engineering. Naturally, the effect is greater the earlier treatment is started. But so far the drug is approved for use only in some countries of Europe, Japan and the USA. Genetic engineering continues to develop in this direction, trying to synthesize and other enzymes required for the normal synthesis and cleavage of glycogen, to help patients with other forms of glycogenosis.
Some patients are helped by the administration of glucocorticoids, anabolic hormones and glucagon. The drugs stimulate some biochemical processes (for example, gluconeogenesis, that is, the process of glucose synthesis from non-carbohydrate substances), thereby reducing the manifestations of the disease.
From surgical methods of treatment in some forms of glycogenoses, the application of portocaval anastomosis or liver transplantation is used. Portocaval anastomosis is applied to patients with severe form of glycogenosis I and III types. It helps to reduce metabolic disturbances, promotes regression of liver size, improves hypoglycemia tolerability. Liver transplantation from the donor is carried out at I, III, IV types of glycogenoses. In the case of type I glycogenesis, the operation is performed only if the dietary therapy measures are ineffective, with type III glycogenesis - when the patient's liver can no longer be saved.
Thus, glycogenoses are a fairly extensive group of metabolic diseases with genetic origins. To date, medicine does not have 100% methods of effective treatment of this disease, the prospects in this direction belong to genetic engineering.