Glucose is a large energy source for the body. It is stored by the body in the form of glycogen and later released into the body with the help of enzymes. Glycogen storage disease (GSD) is a group of inherited disorders where an abnormal amount or type of glycogen is stored in the liver.
Many sugars (including glucose) are present in foods and are used by the body as a source of energy. After a meal, blood glucose levels rise. The body stores the extra glucose that is not needed right away as glycogen in the liver and muscles. Later, as the blood glucose levels in the body begin to dip, the body uses this stored energy. These sugars, stored in the form of glycogen, need to be processed by enzymes in the body before they can carry out their functions.
GSD occurs as a result of the liver's failure to regulate the metabolism of glycogen and glucose. When glucose is changed into glycogen, a different enzyme is required at each step. If one of these enzymes is defective (or missing) and fails to complete its step, the process stops. These enzyme defects cause glycogen storage diseases.
Approximately one in about 20,000 people are affected by glycogen storage diseases. GSD is inherited and occurs because of an inherited defective gene from both parents. If both parents carry the defective gene, there is:
- A 25% chance that their child will develop the disorder
- A 50% chance that their child will receive one defective gene from one of the parents, which means the child will not show symptoms of the disorder but is a "carrier"
- A 25% chance their child will receive both normal genes, one from each parent, and will not have a GSD
There are at least 10 different types of GSDs, which are put into groups based on the enzyme that is missing. The most common forms of GSD are Types I, III and IV.
- GSD I, also known as von Gierkes disease, results from a deficiency of the enzyme Glucose-6-Phosphatase.
- GSD III, also known as Cori Disease, occurs when the enzyme called the debrancher is deficient, causing the body to form glycogen molecules that have an abnormal structure. This abnormal structure also prevents the glycogen from being broken down into free glucose.
- GSD IV, also known as Amylopectinosis, occurs when there is not an increased amount of glycogen in the tissues. Instead, the glycogen that does accumulate has very long outer branches, because there is a genetic deficiency of the branching enzyme. This abnormal glycogen is thought to stimulate the immune system. The result is tremendous scarring (cirrhosis) of the liver as well as other organs, such as muscle and heart.
Symptoms vary based on the enzyme that is missing. They usually result from the buildup of glycogen or from an inability to produce glucose when needed. Because GSD occurs mainly in muscles and the liver, those areas show the most obvious symptoms.
Symptoms may include:
- Growth failure
- Muscle cramps
- Low blood sugar
- A greatly enlarged liver
- A swollen belly
- Abnormal blood test results
The age when symptoms begin and how severe they are depends on the type of GSD.
- Children with GSD I rarely develop cirrhosis (liver disease), but they are at an increased risk for developing liver tumors.
- In some ways, GSD III is a milder version of GSD I. It also is a very rare cause of liver failure, but it may cause fibrosis (early scarring of the liver, which may be caused by a healing response to injury, infection or inflammation).
- GSD II is a muscle disease and does not affect the liver.
- Glycogen storage disease IV causes cirrhosis; it may also cause heart or muscle dysfunction. Often, infants born with GSD IV are diagnosed with enlarged livers and failure to thrive within their first year of life; they develop cirrhosis of the liver by age 3-5.
An exam of a sample of liver tissue is done to tell if a certain enzyme is missing.
Treatment depends on the type of glycogen storage disease. Some GSD types cannot be treated; others are fairly easy to control by treating the symptoms. Patients with treatable GSD do very well if the blood glucose level is maintained within the normal range. Maintaining a healthy blood glucose level can reverse all of the signs of this disease, allowing the child to lead a long, relatively normal life.
In the more severe cases of GSD, infection and other complications are likely to occur. These include liver, heart and respiratory failure. If liver failure occurs, receiving a liver transplant is the only option. Transplants have been effective in reversing the symptoms of GSD.
For the types of GSD that can be treated, patients must carefully follow a special diet:
- Frequent high carbohydrate meals during the day. For some children, eating several small meals rich in sugars and starches every day helps prevent blood sugar levels from dropping.
- Cornstarch. For some young children over the age of 2, giving uncooked cornstarch every four to six hours – including during overnight hours – also can relieve the problem.
- Continuous nighttime feeding. In order to maintain the blood glucose level, a tube is inserted into the stomach each evening to send a solution with a high concentration of glucose. This helps control the blood sugar level. Younger children will have to use this tube each evening, but doctors feel that this may not be necessary once they get older. In the daytime the tube is removed, but the patient must eat foods rich in sugars and starches about every three hours. This treatment can be successful in reversing most symptoms.
- Drug treatment. GSD tends to cause uric acid (a waste product) to accumulate, which can cause gout (painful inflammation of the joints) and kidney stones. Medication is often necessary to prevent this.
In some types of this disease, children must limit their amount of exercise to reduce muscle cramps.