Glycogenosis type 1 was first described in 1929 by Gierke. The disease occurs in one case out of two hundred thousand newborns. Pathology affects equally both boys and girls. Next, consider how Gierke's disease manifests itself, what it is, what therapy is used.
General information
Despite the relatively early discovery, only in 1952 Corey was diagnosed with an enzyme defect. The inheritance of pathology is autosomal recessive. Gierke's syndrome is a disease in which the cells of the liver and convoluted tubules of the kidneys are filled with glycogen. However, these reserves are not available. This is indicated by hypoglycemia and the absence of an increase in blood glucose concentration in response to glucagon and adrenaline. Gierke's syndrome is a disease accompanied by hyperlipemia and ketosis. These signs are characteristic of the state of the body with a deficiency of carbohydrates. At the same time, low activity of glucose-6-phosphatase is noted in the liver, intestinal tissues, kidneys (or it is completely absent).
Course of pathology
How does Gierke's syndrome develop? The disease is caused by defects in the enzyme system of the liver. It converts glucose-6-phosphate into glucose. In case of defects, it is violated asgluconeogenesis and glycogenolysis. This, in turn, provokes hypertriglyceridemia and hyperuricemia, lactic acidosis. Glycogen builds up in the liver.
Girke's disease: biochemistry
In the enzyme system that transforms glucose-6-phosphate into glucose, in addition to itself, there are at least four more subunits. These include, in particular, the regulatory Ca2(+)-binding protein compound, translocases (carrier proteins). The system contains T3, T2, T1, which ensure the transformation of glucose, phosphate and glucose-6-phosphate through the endoplasmic reticulum membrane. There are certain similarities in the types that Gierke's disease has. The clinic of glycogenosis Ib and Ia is similar, in this regard, a liver biopsy is performed to confirm the diagnosis and accurately establish the enzyme defect. The activity of glucose-6-phosphatase is also investigated. The difference in clinical manifestations between type Ib and type Ia glycogenosis is that the former is characterized by transient or permanent neutropenia. In especially severe cases, agranulocytosis begins to develop. Neutropenia is accompanied by dysfunction of monocytes and neutrophils. In this regard, the likelihood of candidiasis and staphylococcal infections increases. Some patients develop inflammation in the intestines, similar to Crohn's disease.
Signs of pathology
First of all, it should be said that Gierke's disease manifests differently in newborns, infants and older children. Symptoms manifest as fasting hypoglycemia. However, in most casespathology is asymptomatic. This is due to the fact that infants often receive nutrition and the optimal amount of glucose. Gierke's disease (photos of the sick can be found in medical reference books) is often diagnosed after birth a few months later. At the same time, the child has hepatomegaly and an increase in the abdomen. Subfebrile temperature and shortness of breath without signs of infection can also accompany Gierke's disease. The causes of the latter are lactic acidosis due to insufficient glucose production and hypoglycemia. Over time, the intervals between feedings increase and a long night's sleep appears. In this case, symptoms of hypoglycemia are noted. Its duration and severity begins to gradually increase, which, in turn, leads to systemic metabolic disorders.
Consequences
In the absence of treatment, changes in the appearance of the child are noted. In particular, muscular and skeletal hypotrophy, slowing down of physical development and growth are characteristic. There are also fatty deposits under the skin. The child begins to resemble a patient who has Cushing's syndrome. At the same time, there are no violations in the development of social and cognitive skills, if the brain was not damaged during repeated hypoglycemic attacks. If fasting hypoglycemia persists and the child does not receive the required amount of carbohydrates, the delay in physical development and growth becomes clearly pronounced. In some cases, children with type I hypoglycenosis die due to pulmonary hypertension. Atplatelet dysfunction recurring nosebleeds or bleeding after dental or other surgery.
There are disorders in platelet adhesion and aggregation. The release of ADP in response to contact with collagen and adrenaline is also impaired. Systemic metabolic disorders provoke thrombocytopathy, which disappears after therapy. Enlargement of the kidneys is detected by ultrasound and excretory urography. Most patients do not have severe renal impairment. At the same time, only an increase in the glomerular filtration rate is noted. The most severe cases are accompanied by tubulopathy with glucosuria, hypokalemia, phosphaturia, and aminoaciduria (like Fanconi's syndrome). In some cases, albuminuria is noted in adolescents. In young people, there is a severe renal lesion with proteinuria, an increase in pressure and a decrease in creatinine clearance, which is due to interstitial fibrosis and focal segmental glomerulosclerosis. All these violations provoke end-stage renal failure. The size of the spleen remains within the normal range.
Liver adenomas
They occur in many patients for various reasons. They usually appear between the ages of 10 and 30. They can become malignant, hemorrhages into the adenoma are possible. These formations on scintigrams are presented as areas of reduced accumulation of the isotope. Used to detect adenomasultrasound procedure. In case of suspicion of a malignant neoplasm, more informative MRI and CT are used. They make it possible to trace the transformation of a clear limited formation of a small size into a larger one with rather blurred edges. At the same time, periodic measurement of serum levels of alpha-fetoprotein (a marker of liver cell cancer) is recommended.
Diagnosis: Mandatory Research
Uric acid, lactate, glucose levels, liver enzyme activity on an empty stomach are measured for patients. In infants and newborns, the concentration of glucose in the blood after 3-4 hours of fasting decreases to 2.2 mmol / liter or more; with a duration of more than four hours, the concentration is almost always less than 1.1 mmol / liter. Hypoglycemia is accompanied by a significant increase in lactate and metabolic acidosis. Whey is usually cloudy or milky due to very high triglyceride concentrations and moderately elevated cholesterol levels. There is also an increase in the activity of AlAT (alanine aminotransferase) and AsAT (aspartaminotransferase), hyperuricemia.
Provocative auditions
To differentiate type I from other glycogenoses and accurately determine the enzyme defect in infants and older children, the level of metabolites (free fatty acids, glucose, uric acid, lactate, ketone bodies), hormones (STH (somatotropic hormone), cortisol, adrenaline, glucagon, insulin) after glucose and on an empty stomach. The study is carried out according tocertain scheme. The child receives glucose (1.75 g/kg) orally. Then every 1-2 hours a blood sample is taken. The glucose concentration is quickly measured. The last analysis is taken no later than six hours after taking glucose or when its content has decreased to 2.2 mmol / liter. A provocative test with glucagon is also carried out.
Special Studies
During them, a liver biopsy is performed. Glycogen is also being examined: its content is significantly increased, but the structure is within the normal range. Measurements of glucose-6-phosphatase activity are carried out in destroyed and whole liver microsomes. They are destroyed by repeated freezing and thawing of the biopath. Against the background of type Ia glycogenosis, activity is not determined either in destroyed or intact microsomes, in type Ib it is normal in the first, and in the second it is significantly reduced or absent.
Girke's disease: treatment
In type I glycogenosis, metabolic disorders associated with insufficient glucose production appear after a meal several hours later. With prolonged fasting, the disorders are greatly intensified. In this regard, the treatment of pathology is reduced to the frequency of feeding the child. The goal of therapy is to prevent a fall in glucose below 4.2 mmol/liter. This is the threshold level at which the secretion of contrasular hormones is stimulated. If the child receives a sufficient amount of glucose in a timely manner, there is a decrease in the size of the liver. At the same time, laboratory parameters are approaching the norm, and psychomotor development and growthstabilized, bleeding disappears.
