Type 1 glycogenosis was first described in 1929 by Girke. The disease occurs in one case out of two hundred thousand newborns. Pathology affects equally both boys and girls. Next, we consider how Girke's disease manifests itself, what is it, what kind of therapy is used.
General information
Despite a relatively early detection, it was not until 1952 that Corey discovered an enzyme defect. Inheritance of pathology is autosomal recessive. Girke's syndrome is a disease against 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. Girke'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, a low glucose-6-phosphatase activity is noted in the liver, intestinal tissues, and kidneys (or it is completely absent).
Pathology
How does Girke's syndrome develop? The disease is caused by defects in the liver enzyme system. It converts glucose-6-phosphate into glucose. With defects, both gluconeogenesis and glycogenolysis are disrupted. This, in turn, provokes hypertriglyceridemia and hyperuricemia, lactic acidosis. Glycogen accumulates in the liver.
Girke's disease: biochemistry
In the enzyme system, which transforms glucose-6-phosphate into glucose, in addition to itself, there are at least four more subunits. These include, in particular, regulatory Ca2 (+) - a 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 between the types of Girke's disease. The clinic of glycogenosis Ib and Ia is similar, in connection with this, a liver biopsy is performed to confirm the diagnosis and accurately establish the enzyme defect . Glucose-6-phosphatase activity is also being investigated. The difference in the clinical manifestations between type Ib and Ia glycogenosis is that, at the first, transient or permanent neutropenia is noted. 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. In some patients, inflammation appears in the intestines, similar to Crohn's disease.
Signs of pathology
First of all, it should be said that in newborns, infants and older children, Girke's disease manifests itself differently. Symptoms manifest as hypoglycemia starvation. However, in most cases, the pathology is asymptomatic. This is due to the fact that infants often receive nutrition and the optimal amount of glucose. Girke's disease (photos of patients can be found in medical guides) are often diagnosed after birth a few months later. In this case, hepatomegaly and an increase in the abdomen are detected in the child. Low-grade fever and shortness of breath without signs of infection can also accompany Girke's disease. The reasons for 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 metabolic disorders of the systemic type.
Effects
If untreated, changes in the appearance of the child are noted. In particular, muscular and skeletal hypotrophy, a slowdown in physical development and growth are characteristic. Fat deposits under the skin are also observed. The child begins to resemble a patient who has Cushing's syndrome. In this case, there are no violations in the development of social and cognitive skills, if during repeated hypoglycemic attacks the brain was not damaged. If hypoglycemia of starvation 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 hypoglycaenosis die due to pulmonary hypertension. If platelet function is impaired, repeated nosebleeds or bleeding occurs after a dental or other surgical intervention.
Disorders are observed with adhesion and platelet 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. Kidney enlargement is detected by ultrasound and excretory urography. Most patients do not have severe renal impairment. Moreover, only an increase
in glomerular filtration rate is noted
. The most severe cases are accompanied by tubulopathy with glucosuria, hypokalemia, phosphaturia and aminoaciduria (similar to
Fanconi syndrome). In some cases, adolescents have albuminuria. In young people, there is a severe renal failure with proteinuria, an increase in pressure and a decrease in creatinine clearance, which is due to interstitial fibrosis and focal segmental glomerulosclerosis. All these disorders provoke terminal renal failure. The size of the spleen remains within normal limits.
Liver adenomas
They occur in many patients for various reasons. As a rule, they appear at the age of 10 to 30 years. They can be malignant, hemorrhages in the adenoma are possible. These scintigram formations are represented as sections of a reduced isotope accumulation. An ultrasound scan is used to detect adenomas. If a malignant neoplasm is suspected, more informative MRI and CT are used. They allow us to trace the transformation of a clear, limited formation of a small size into a larger one with sufficiently blurred edges. A periodic measurement of serum alpha-fetoprotein (a marker of liver cancer) is recommended.
Diagnosis: compulsory research
Patients measure uric acid, lactate, glucose, and fasting liver enzyme activity. In infants and newborns, the glucose concentration in the blood after 3-4 hours of starvation is reduced 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. Serum is usually cloudy or similar to milk due to a very high concentration of triglycerides and moderately elevated cholesterol. There is also an increase in the activity of AlAT (alanine aminotransferase) and AsAT (aspartamenotransferase), hyperuricemia.
Provocative tests
To differentiate type I from other glycogenoses and to accurately determine the enzyme defect in infants and older children, the level of metabolites (fatty free acids, glucose, uric acid, lactate, ketone bodies), hormones (STH (somatotropic hormone), cortisol, adrenaline, glucagon is measured , insulin) after glucose and on an empty stomach. The study is carried out according to a certain scheme. The child receives glucose (1.75 g / kg) by mouth. Then, every 1-2 hours, blood is drawn. Glucose concentration is quickly measured. The last analysis is taken no later than six hours after glucose intake or when its content has decreased to 2.2 mmol / liter. A provocative test with glucagon is also performed.
Special studies
During them, a liver biopsy is performed. Glycogen is also being investigated: its content is significantly increased, but the structure is within normal limits. Measurements of glucose-6-phosphatase activity in destroyed and whole liver microsomes are carried out. They are destroyed by repeated freezing and thawing of the biopat. Against the background of type Ia glycogenosis, activity is not determined either in destroyed or in whole microsomes; in type Ib, in the former it is normal, and in the latter it is significantly reduced or absent.
Girke's disease: treatment
With type I glycogenosis, metabolic disorders associated with insufficient glucose production appear after eating a few hours later. With prolonged starvation, the disorder increases significantly. In this regard, the treatment of pathology is reduced to the frequent feeding of the child. The goal of therapy is to prevent a drop in glucose below 4.2 mmol / liter. This is the threshold level at which the secretion of counter-hormonal hormones is stimulated. If the child receives a sufficient amount of glucose in a timely manner, a decrease in liver size is noted. At the same time, laboratory indicators are approaching normal, and psychomotor development and growth are stabilized, bleeding disappears.