Von Gierke disease is the most common glycogen storage disease. The disease is characterized by the unavailability of glycogen reserves in the liver. However, the stored glycogen in the muscles is not affected.
What is Von Gierke disease
Von Gierke disease was first described by doctor Edgar von Gierke in 1929. In this disease, the glycogen stored in the liver can no longer be used due to a genetic defect. A few hours after eating, the blood sugar level drops dangerously, which must be compensated for immediately with readily available carbohydrates. For keel chest (kc), please visit nonprofitdictionary.com.
Glycogen is a polysaccharide like vegetable starch, which is broken down into monosaccharides during periods of starvation and returned to the body in the form of glucose. In addition, this reduction keeps the blood sugar level constant. Due to a mutation, the responsible enzyme glucose-6-phosphatase is no longer produced sufficiently or only in an inactive form. This genetic defect is inherited in an autosomal recessive manner.
The disease is very rare. Only about one in 100,000 newborns suffers from this disease. However, Von Gierke disease is the most common glycogen storage disease. It is also called glycogen storage disease type I (GSD1) or glycogenosis type I. However, the syndrome can still be divided into types Ia and Ib. Type Ia occurs at 80 percent and type Ib at 20 percent.
Causes
The cause of von Gierke disease is a genetic defect in the G6PC gene on chromosome 17 in type Ia and a genetic defect in the SLC37A4 gene on chromosome 11 in type Ib. Both gene mutations are inherited in an autosomal recessive manner. In type Ia, the enzyme glucose-6-phosphatase is no longer available in sufficient quantities or is ineffective due to a defect. This enzyme is responsible for breaking down glucose-6-phosphate, releasing glucose and the phosphate group.
Glucose-6-phosphate is a metabolite in the glycogen-to-glucose breakdown chain. Due to the lack of dephosphorylation of this compound, the glucose cannot form. It merely prompts further synthesis of glycogen. The glycogen stores in the liver fill up more and more. This leads to their enlargement ( hepatomegaly ). At the same time, the blood sugar level can no longer be balanced. After the meal, the blood sugar is pumped into the cells for burning by the action of insulin.
When blood sugar gets too low, glucagon, the antagonist of insulin, is produced in excess. Glucagon breaks down glycogen reserves in the liver and muscles. If the enzyme glucose-6-phosphatase is defective, glucagon can no longer cause the formation of glucose from glycogen.
In von Gierke disease type Ib, a different enzyme is primarily affected by a defect. It is a transport enzyme of glucose-6-phosphatase. Although the glucose-6-phosphatase is intact here, it cannot be transported to its destination, the liver.
Symptoms, Ailments & Signs
Von Gierke disease is characterized by hepatomegaly (enlarged liver), elevated blood glucose levels after eating, and severely decreased blood glucose levels after three hours of fasting. At the same time, there is an increased uric acid level and increased triglyceride levels in the blood. If food is not eaten, hypoglycemic seizures occur.
The disease is already noticeable in children as young as three to four months. Growth is delayed. At the same time, osteopenia or osteoporosis occurs. The face appears round with full cheeks. In addition to the liver, the kidneys are also enlarged. In addition, frequent nosebleeds occur due to platelet dysfunction.
In type Ib, there are also functional disorders of the neutrophils. This is why frequent infections and intestinal inflammation develop. Liver dysfunction due to liver adenomas or even liver carcinoma can occur as late complications. Renal insufficiency can also develop.
Diagnosis & course of disease
Von Gierke disease can be diagnosed very well by the typical course of the blood sugar curve in connection with the lactate level. Hyperglycemia and hypolactacidemia are always present immediately after meals. After three to four hours of fasting, the blood sugar level is too low and the lactate level is too high.
Hypoglycemia in von Gierke disease is always fasting dependent. The activity of glucose-6-phosphatase is only rarely determined today. Because this necessity is eliminated by molecular genetic studies. Liver tumors can be excluded in the differential diagnosis using imaging methods. The other glycogenoses can also be clearly distinguished, because they show high blood sugar values and high lactate values after meals and after three to four hours correspondingly low blood sugar values and low lactate values.
Complications
In von Gierke disease, patients primarily suffer from a severe enlargement of the liver. This can also cause pain as the liver presses on the other organs. Severely reduced blood sugar levels also occur as a result of illness and have a very negative effect on the quality of life of those affected.
The patients are unable to carry out strenuous activities or sporting activities and often feel tired or exhausted. Von Gierke disease also causes a significantly reduced resilience. Those affected suffer from cramps in the muscles and, in many cases, from nosebleeds. The disease can also lead to inflammation in the intestines or liver. In the worst case, a tumor forms in the liver.
Von Gierke’s disease can also lead to kidney failure, so that patients are dependent on dialysis or a kidney transplant in their lifetime. Since the causal treatment of Von Gierke disease is not possible, only the individual symptoms are treated. Complications do not arise. However, the life expectancy of the patient is significantly reduced and limited by the disease.
When should you go to the doctor?
Since Von Gierke’s disease cannot heal on its own, those affected by this disease definitely need to see a doctor. This is the only way to prevent further complications and symptoms, so that a doctor should be consulted at the first signs and symptoms of the disease. An early diagnosis has a very positive effect on the further course of this disease. In most cases, the doctor should be contacted if the person concerned permanently suffers from high blood sugar levels.
A significantly enlarged liver is usually a sign of this disease. Most of those affected also have frequent nosebleeds or suffer from intestinal problems. If these symptoms occur over a longer period of time and do not go away on their own, a doctor must be contacted in any case. As a rule, Von Gierke disease can be diagnosed by a general practitioner or an internist. However, further treatment always depends on the exact severity of the symptoms. It cannot be universally predicted whether the disease will lead to a reduced life expectancy.
Treatment & Therapy
Von Gierke disease is treated symptomatically. The aim is to avoid hypoglycaemia through short periods of fasting. Small and carbohydrate-rich meals must be taken frequently during the day. During the night, a permanent supply of a dextrin solution via tubes is required.
Early treatment can prevent later organ damage. In addition, the children can achieve normal growth. However, if severe liver and kidney damage occurs despite this, an organ transplant must also be considered.
Prevention
Human genetic counseling should be carried out in affected families to prevent von Gierke disease. If cases have already occurred in family and relatives, human genetic tests are available. The disease is inherited in an autosomal recessive manner.
If both parents each have a defective gene, the offspring has a 25 percent chance of suffering from Von Gierke disease. However, if only one parent has the defective gene, the children are unlikely to develop the disease.
Aftercare
Direct follow-up care is only possible to a limited extent in von Gierke’s disease. Due to the mostly genetic causes, a causal treatment is not very promising. However, a genetic test is recommended if there is a desire to have children. In this way, a recurrence of the symptoms and the course of the disease can be prevented. The best chance of relief after therapeutic treatment is to see a doctor as early as possible, as soon as symptoms appear.
There are now medications that can slow the progression. Exact adherence to the dosage is important for effective aftercare. Regular check-ups are part of the schedule. In this way, the current status of the clinical picture can be recognized and, if necessary, positively influenced by changing the dosage or changing the medication.
Patients with Von Gierke disease can also influence the course of the disease themselves. It is important to rest and take care of yourself after a treatment. This will help relieve symptoms. Emotional stability and avoiding stressful situations also help slow the heart rhythm.
At the same time, this means that the organs have to withstand less pressure. Overall, the entire organism is spared. With regard to nutrition, cholesterol intake should be avoided for long-term follow-up care. Extreme caution is also required with greasy ingredients. The body’s immune system remains more stable through daily exercise in the fresh air.
You can do that yourself
Von Gierke disease must be treated in a pediatric metabolic center. Affected children must follow an adapted diet in order to reduce the symptoms of Von Gierke disease. In addition to the inpatient treatment, which includes glucose treatment in the form of maltodextrin, the patients have to take it easy. Parents of affected children should also pay attention to typical symptoms such as bleeding or liver problems and inform the doctor about them.
Von Girke disease is a serious condition that requires constant monitoring. This can be a heavy burden for parents or guardians. Worries and fears can be dealt with as part of therapy. In addition, contact should be made with other parents in whose family there is a case of Von Gierke disease.
The external changes such as short stature or the typical doll face can be treated surgically. After a surgical procedure, the hygiene measures prescribed by a doctor must be observed. Abdomen should be evaluated promptly by a doctor to avoid internal bleeding and other complications. Comprehensive self-help can at least enable those affected to have a symptom-free everyday life. Medical treatment by an internist is always a prerequisite.
