Jul 16, 2018
Glycogenosisis a hereditary pathology associated with an inadequate content of a specific enzyme that takes mediated participation in the synthesis and destruction of glycogen. As a result of the above-mentioned disorders, conditions are created for excessive accumulation in the hepatic parenchyma and muscle tissue of glycogen.
Glycogenoses of the cause of
Under the condition of the normal functioning of the human body's enzyme system, the process of glucose breakdown, which in some cases in excess amounts comes with food, occurs with the formation of a certain supply of glycogen in the hepatic parenchyma and muscle fibers. Glycogen is a rapidly transformed substance, which under necessary conditions is split with the reverse formation of glucose and its entry into the bloodstream.
The main pathogenetic mechanism of glycogenesis development is the appearance of a defective enzyme involved in the process of glycogen exchange. As a result of these disorders, either excessive formation of glycogen and its increased concentration in tissues, or a violation of its decay and reverse glucose formation, occurs.
There is another form of glycogenesis, when, on the contrary, a defective enzyme does not allow the synthesis of glycogen and its insufficient content in "typical storage tissues", the so-called aglycogenosis.
Some forms of glycogenosis are accompanied by severe symptoms of hypoglycemia caused by a violation of glucose synthesis from their own glycogen stores in various stress situations.
Glycogenoses in children are significantly more frequent than in the adult population, since this disease belongs to the category of hereditary congenital disorders and the debut of clinical manifestations is the period of newborns.
Clinical manifestations of the disease are specific for each type of glycogenosis, but there is a large group of symptoms characteristic of all forms of this pathology:
is a progressive significant increase in liver parameters, and in some cases, spleen, detected palpation, and also with the help of beam instrumental research methods;
- generalized or limited decrease in muscle tone with increased convulsive readiness;
- respiratory disorders in the form of progressive dyspnea and hypoxia;
- neurological symptoms of focal and cerebral nature;
- pronounced lag of the bone type of age from the passport one and complete absence of intellectual-mnestic disorders;
- nephropathy, caused by excessive accumulation of uric acid, which contributes to the formation of concrements in the calyx-pelvis kidney system.
Diagnosis of glycogenoses in a newborn child in most situations is not difficult, but to confirm the diagnosis, a study of the patient's glycemic and lactatemic profile is recommended, and in difficult cases, the use of biopsy methods of the muscle or liver parenchyma to study the activity of enzymes taking mediated participation in metabolic glucose conversions.
Depending on the nature of enzyme deficiency, as well as the predominance of glycogen accumulation in muscle tissue or in the hepatic parenchyma, it is common to divide all glycogenases into several types.
Glikogenozy and aglykogenozy, belonging to the 0 type, are accompanied by the development of a symptom of a complex of hypoglycemic coma that occurs against the background of a complete lack of a minimum reserve of glycogen in the liver parenchyma.
→ Hereditary disease Girke or type 1 glycogenosis is transmitted from generation to generation, provided that both parents have phenotypic manifestations of this pathology or will be carriers of the defective gene. The clinical symptomatic complex of this type of glycogenesis is due to the insufficient content of the enzyme involved in the cleavage and synthesis of glycogen in the mucous membrane of the small intestine, liver and kidneys. The debut of the emergence of a clinical picture occurs during the period of newborns and is accompanied by the development of respiratory distress syndrome, hypoglycemic convulsive syndrome, impaired digestibility of food and indomitable gag reflex. During a short period of time, the child shows signs of an increase in glycogen infiltration in the liver and kidneys, accompanied by pronounced increases in their size and shape disruption. Phenotypic features of children suffering from type 1 glycogenosis are: disproportionality of development of various parts of the body, delay in the appearance of secondary sexual characteristics, generalized decrease in muscle tone.
→ Autosomal recessive hereditary disease Pompe, or type 2 glycogenosis, is characterized by a fast-progressive course and the onset of the first symptoms of the disease in the first days after the birth of the child. The severe course of the disease with pronounced disturbances in the functioning of all structures of the child's organism is due to the fact that the defect of the enzyme participating in metabolic metabolism of glycogen is observed not only in the muscle tissue, but also in all internal organs and blood cells. A distinctive feature of this form of glycogenosis is the defeat of the heart muscle, which leads to marked hypertrophic cardiomyopathy and a significant increase in the parameters of all parts of the heart. Signs of the defeat of the respiratory system are the propensity to develop hypostatic pneumonia and segmental atelectasis, manifested by symptoms of respiratory failure and infectious and inflammatory symptoms. The most pronounced manifestations of type 2 glycogenesis are related to muscle tissue and are characterized by the development of a clinic of spastic myopathy( decreased muscle tone, lack of response in the study of tendon reflexes, paralysis).
→ Hereditary Cory pathology, or type 3 glycogenosis, traditionally has an autosomal recessive type of inheritance and is characterized by the appearance of an enzymatic defect in the hepatic, muscle tissue, and also in blood cells. A peculiarity of this form of glycogenosis is the emergence of a characteristic clinical picture after a six-month-old age and a significant regression of the disease after the child reaches the age of five, therefore, this type of disease refers to a pathology having the most favorable outcome of the disease. With glycogenesis of type 3, the structures of muscle fibers of skeletal muscles are more affected, therefore the main, and sometimes the only manifestations become: limited adynamia, hypotonia and hyporeflexia of muscles.
→ Type 4 glycogenesis, or Andersen's disease, is characterized by a severe progressive lesion of the hepatic parenchyma with the development of irreversible changes in the form of cirrhotic tissue proliferation accompanied by a pronounced impairment of the protein-synthetic and other vital liver functions. In addition to inheritance by recessive type, there is a clear dependence on gender.
→ Myophosphorylase deficiency, or type 5 glycogenosis, is characterized by an isolated lesion of muscle fibers of skeletal muscles, which is why the main manifestations of this type of pathology are limb deformations caused by uneven limited hypertrophy of muscle tissue in one area or another, as well as a pronounced convulsive syndrome. The appearance of this type of glycogenosis has a connection with gender, that is, it is observed only in boys. Diagnosis of type 5 glycogenesis is not difficult, since the elementary analysis of urine and blood have characteristic changes( transitory myoglobulinuria and a decrease in the concentration of lactate in the blood during a sample with physical exertion).
→ Autosomal recessive hereditary GERS disease, or type 6 glycogenosis, debuts in infancy and is characterized by isolated liver damage with concomitant hyperglycemia and hyperlipemia.
→ Glycogenosis type 7, or hereditary Tarui disease, has manifestations similar to glycogenase type 5.
→ A feature of type 8 glycogenosis, or Thomson's disease, is the defeat of the nervous system, the damage to the liver parenchyma, as a result of which, in the first year after birth, the phenomena of cerebral and focal neurological symptoms increase. This pathology has recently been extremely rare and has no connection with the genetic type of inheritance.
→ Type 9 glycogenosis is found exclusively in boys and is characterized by an autosomal recessive type of inheritance. The only manifestations of this pathology is progressive hepatomegaly.
→ Type 10 glycogenosis is represented by a single episode, therefore the fact of transmission of predisposition to this pathology is not revealed and at present this type of glycogenosis does not occur.
→ Type 11 glycogenosis is extremely rare and is accompanied by all the symptoms that are characteristic of all forms of glycogenesis. A feature of this type is the appearance in the child of signs of rickets associated with a deficiency of phosphorus in the blood and leveling of these symptoms with the onset of puberty.
The priority in the treatment of glycogenosis of one type or another is the correction and prevention of hypoglycemic manifestations by medication and non-medicamentous measures.
Non-pharmacological treatment of hypoglycemia involves correction of eating behavior with the preferred daily intake of easily-split types of carbohydrates and increased amounts of proteins, while limiting physical exertion.
Given the pathogenetic features of the onset of the disease, the patient should be prepared to ensure that full recovery, even if all possible methods of treatment are applied, will not occur. In this regard, treatment activities are aimed at improving the patient's well-being and preventing possible complications.
Each of the individual types of glycogenesis needs an individual approach to the treatment. Thus, children with type 1 glycogenosis show the use of water-soluble vitamin D( Aquadetrim 1-2 caps / day during the first year of life).Due to the fact that this type of glycogenosis is accompanied by the development of signs of nephropathy, a reduction in the concentration of uric acid is recommended, so it is expedient in this case to prescribe Allopurinol. For the prevention of stone formation in the lumen of the gallbladder, which develops when the level of triglycerides in the blood increases, it is necessary to administer nicotinic acid. Severe neutropenia needs correction by the method of prescribing a long course of colony-stimulating factor( Filgrastim in the minimum daily dosage of 2.5 mg per kg of body weight of the child) with mandatory control of the treatment by laboratory diagnostic methods.
Currently, in the era of the development of genetic engineering technology, the development of drugs that could be used as a replacement therapy for glycogenesis is being actively pursued. In the US and many European countries, positive results of enzyme replacement therapy for type 2 glycogenosis were obtained with the use of myosin at a dosage of 20 mg per kg of body weight 2 p / mo for a long course. This drug is aimed at reducing cardiomegaly, as well as improving the functioning of the muscular system.
Surgical methods of treatment find their application only in the case of the development of irreversible damage to the hepatic parenchyma, observed in types 3 and 4 types of glycogenoses, and are the product of liver transplantation. Muscular forms of glycogenoses, accompanied by progressive myopathy and cardiomegaly, are not an indication for surgical treatment.