Gyrke disease: causes, symptoms, treatment

Glycogenosis type 1 was first described in 1929 by Girke. The disease occurs in one case of two hundred thousand newborns. Pathology affects both boys and girls alike. Next, let's look at how Girke's disease manifests, what it is, what therapy is used.

General information

Despite the relatively early detection, only in 1952, Corey was diagnosed with an enzyme defect. Inheritance of pathology is autosomal recessive. Girke syndrome is a disease against which the liver cells and convoluted tubules of the kidneys are filled with glycogen. However, these reserves are inaccessible. This is indicated by hypoglycemia and the absence of an increase in blood glucose concentrations in response to glucagon and epinephrine. Girke syndrome is a disease accompanied by hyperlipemia and ketosis. These signs are characteristic for the state of the body with a deficiency of carbohydrates. At the same time in the liver, intestinal tissues, kidneys there is a low activity of glucose-6-phosphatase (or it is completely absent).

Course of pathology

How does the Girke syndrome develop? The disease is caused by defects in the enzyme system of the liver. It turns glucose-6-phosphate into glucose. With defects, both gluconeogenesis and glycogenolysis are disturbed. This, in turn, provokes hypertriglyceridemia and hyperuricemia, lactic acidosis. The liver accumulates glycogen.

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, providing the transformation of glucose, phosphate and glucose-6-phosphate through the membrane of the reticulum of the endoplasm. There are certain similarities in the types that Hirke's disease has. The clinic for glycogenesis Ib and Ia is similar, therefore a liver biopsy is performed to confirm the diagnosis and to accurately establish the enzyme defect . The activity of glucose-6-phosphatase is also investigated. The difference in clinical manifestations between glycogenesis of type Ib and Ia is that at the first there is a transient or constant neutropenia. In especially severe cases, agranulocytosis begins to develop. Neutropenia is accompanied by dysfunction of monocytes and neutrophils. In connection with this, the likelihood of candidiasis and staphylococcal infections increases. Individual patients develop inflammation in the intestine, 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 is differently manifested. Symptoms manifest in the form of fasting hypoglycemia. However, in most cases, the pathology is asymptomatic. This is due to the fact that infants often receive food and the optimal amount of glucose. Disease Girke (photos of cases can be found in medical reference books) is often diagnosed after birth a few months later. The child thus reveals hepatomegaly and an enlarged abdomen. Subfebrile temperature and shortness of breath without signs of infection can also accompany Girke's disease. The causes of the latter - lactic acidosis due to inadequate glucose production and hypoglycemia. Over time, the intervals between feedings increase and there is a prolonged night's sleep. In this case, the symptoms of hypoglycemia are noted . Its duration and severity begins to increase gradually, which, in turn, leads to metabolic disorders of the systemic type.

Effects

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 fat 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 hypoglycosis die due to pulmonary hypertension. If the function of platelets is disturbed, repeated nasal bleeding or bleeding after dental or other surgical intervention is observed. Disturbances are observed in the adhesion and aggregation of platelets. Also, the release of ADP in response to contact with collagen and adrenaline is impaired. Systemic metabolic disturbances provoke thrombocytopathy, which disappears after therapy. Enlargement of the kidneys is revealed with ultrasound and excretory urography. In most patients, there is no marked renal impairment. At the same time there is only an increase in the glomerular filtration rate. The most severe cases are accompanied by tubulopathy with glucosuria, hypokalemia, phosphaturia and aminoaciduria (type of Fanconi syndrome). In some cases, adolescents have albuminuria. Young people have renal damage to the severe course with proteinuria, increased blood pressure and decreased creatinine clearance, which is due to interstitial fibrosis and glomerulosclerosis of a focal-segmental nature. All these disorders provoke terminal renal failure. The size of the spleen remains within normal limits.

Liver adenoma

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 to the adenoma are possible. These formations on scintigrams are presented in the form of areas of reduced isotope accumulation. For the detection of adenomas, ultrasound is used. In case of suspicion of malignant neoplasm, 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. It is recommended that periodic measurement in serum levels of alpha-fetoprotein (a marker of cancer of liver cells).

Diagnostics: compulsory research

Patients are measured levels of uric acid, lactate, glucose, activity of hepatic enzymes on an empty stomach. In infants and newborns, the concentration of glucose in the blood after 3-4 hours of fasting 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 turbid or similar to milk due to a very high concentration of triglycerides and moderately increased levels of cholesterol. There is also an increase in the activity of AlAT (alanine aminotransferase) and AsAT (aspartame aminotransferase), hyperuricemia.

Provocative tests

For the differentiation of type I from other glycogenoses and the precise determination of the enzyme defect in infants and children, the level of metabolites (fatty free acids, glucose, uric acid, lactate, ketone bodies), hormones (STH (somatotropic hormone), cortisol, adrenaline, glucagon , Insulin) after glucose and on an empty stomach. The research is carried out according to a certain scheme. The child receives glucose (1.75 g / kg) orally. Further, blood is drawn every 1-2 hours. The concentration of glucose is rapidly measured. The last analysis is taken no later than six hours after the intake of glucose or when its content decreased to 2.2 mmol / liter. A provocative test with glucagon is also conducted.

Special researches

During these, a liver biopsy is performed. Also glycogen is investigated: its content is significantly increased, but the structure is within the limits of the norm. Measurements of the activity of glucose-6-phosphatase in destroyed and whole liver microsomes are carried out. 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 whole microsomes, in type Ib - in the first it is normal, and in the second it is significantly reduced or absent.

Girke's disease: treatment

With type I glycogenosis, metabolic disorders associated with inadequate production of glucose appear after eating several hours later. With prolonged starvation, the disorders significantly increase. In connection with this, the treatment of pathology is reduced to the increase in the feeding of the child. The goal of the therapy is to prevent a drop in glucose below 4.2 mmol / liter. This is the threshold level at which the secretion of the contrusular hormones is stimulated. If a child receives a timely enough volume of glucose, there is a decrease in liver size. Laboratory indicators in this case are close to normal, and psychomotor development and growth stabilize, bleeding disappears.