Glycogen Storage Disease (GSD)
What is glycogen and glycogen storage disease (GSD)?
The body’s cells need a steady supply of fuel in order to function the right way. This fuel is a simple sugar called glucose. Glucose comes from breaking down the food we eat. The body uses as much glucose as it needs to function and stores the rest to use later.
Before it can be stored, the body must combine the simple glucose units into a new, complex sugar called glycogen. The glycogen is then stored in the liver and muscle cells. When the body needs extra fuel, it breaks down the glycogen stored in the liver back into the glucose units the cells can use. Special proteins called enzymes help both make and break down the glycogen in a process called glycogen metabolism.
Sometimes a person is born missing an enzyme needed for this process or it may not work right. Then the body is not able to store or break down the glycogen as it should. This can lead to very low blood glucose levels during periods of fasting. The muscles and organs need a certain level of glucose in the blood to work properly.
When the body is missing an enzyme or has a flawed enzyme and is not able to use glycogen the right way, it leads to a condition called glycogen storage disease (GSD). Many different enzymes are used by the body to process glycogen. And, as a result, there are several types of GSD.
What are the types of GSD?
Each type of GSD centers on a certain enzyme or set of enzymes involved in glycogen storage or break down. There are at least 13 types of glycogen storage disease. Doctors know more about some types than others. GSD mostly affects the liver and the muscles. Some types cause problems in other areas of the body as well. Types of GSD and the parts of the body they affect the most include:
- Type 0 (Lewis' disease) – Liver.
- Type I (von Gierke’s disease) Type Ia – Liver, kidneys, intestines; Type Ib – Liver, kidneys, intestines, blood cells.
- Type II (Pompe’s disease) – Muscles, heart, liver, nervous system, blood vessels.
- Type III (Forbes-Cori disease) – Liver, heart, skeletal muscles, blood cells.
- Type IV (Andersen’s disease) – Liver, brain, heart, muscles, skin, nervous system.
- Type V (McArdle’s disease) – Skeletal muscles.
- Type VI (Hers’ disease) – Liver, blood cells.
- Type VII (Tarui’s disease) – Skeletal muscles, blood cells.
- Type IX – Liver.
- Type XI (Fanconi-Bickel syndrome) – Liver, kidneys, intestines.
How common are they?
A glycogen storage disorder occurs in about one in 20,000 to 25,000 babies. The most common types of GSD are types I, II, III, and IV, with type I being the most common. It is believed that nearly 90% of all patients with GSD have types I through IV. About 25% of patients with GSD are thought to have type I. However, GSD types VI and IX can have very mild symptoms and may be underdiagnosed.
Most of the severe forms of GSD are diagnosed in babies and children. Some of the milder types might not be found until the person is an adult.
Symptoms and Causes
What are the symptoms of glycogen storage disease (GSD)?
Symptoms vary based on the type of GSD. Some GSDs affect mostly the liver. These include Types 0, I, III, IV, VI and IX. However, they may sometimes have overlapping symptoms affecting muscle and heart. These types (except for GSD type 0) may cause the liver to become enlarged. An enlarged liver is linked to low blood glucose levels because excess glycogen is stored in the liver instead of being released as glucose in the blood stream. Symptoms of low blood glucose, or hypoglycemia, include sweating, tremor, drowsiness, confusion and sometimes seizures. Some GSDs, such as types V and VII, mostly affect the skeletal muscles. Muscle weakness and muscle cramps are the most common symptoms of these types.
Other symptoms that may occur include:
- Very slow growth.
- Obesity (being very overweight).
- Problems with bleeding and blood clotting.
- Kidney problems.
- Low resistance to infections.
- Breathing problems.
- Heart problems.
- Mouth sores.
What causes GSDs?
GSDs occur when there is a problem with the gene that has the instructions for making the enzyme that is missing or not working right. The gene is passed down from parents to children. In most cases, in order to have the GSD, a child must get a bad gene from both parents. Just because both parents have the gene does not always mean they will both pass it on to their children.
Diagnosis and Tests
How are types of glycogen storage diseases (GSDs) detected?
There are four symptoms that might cause the doctor to suspect a type of GSD that affects the liver.
- A low blood glucose level.
- An enlarged liver.
- Lagging growth.
- Abnormal blood tests.
Because GSDs can run in families, a thorough medical history can also give the doctor a first clue. He or she may suggest some tests that might include:
- Blood tests – To find out your blood glucose level and to see how your liver, kidneys and muscles are working.
- Abdominal ultrasound – To see if your liver is enlarged.
- Tissue biopsy – Testing a sample of tissue from a muscle or your liver to measure the level of glycogen or enzymes present.
- Gene testing – To look for problems with the genes for different enzymes. Gene testing can confirm a GSD.
Management and Treatment
How is glycogen storage disease (GSD) treated?
Treatment varies depending on the type of GSD. For types of GSD that involve the liver, treatment is aimed at keeping the right level of glucose in the blood. This is often enough to maintain the cells fuel needs and prevent long-term complications associated with poorly controlled GSD. Treatment consists of taking regular doses of uncooked cornstarch and/or nutrition supplements. Cornstarch is a complex carbohydrate that is difficult for the body to digest; therefore it maintains normal blood sugar levels for a longer period of time than most carbohydrates in food. Eating many small meals that are low in sugar can help keep blood sugar levels normal while preventing excess glycogen storage in the liver.
Carbohydrate solutions may be given continuously during the night to prevent a drop in blood glucose level during sleep, but this carries more risk of severe hypoglycemia compared to using uncooked cornstarch around the clock.
Type IV GSDs with progressive liver disease may have to be considered for liver transplantation after a thorough evaluation.
Can glycogen storage disease (GSD) be prevented?
GSDs are handed down from parents to children through their genes. Therefore, they cannot be prevented. Parents can find out through genetic testing if they carry a gene for a GSD. Both parents must have a gene for the same type of GSD for a child to inherit the disorder.
Outlook / Prognosis
What is the outlook for someone with a glycogen storage disease (GSD)?
The outlook depends on the type of GSD and the organs that are affected. Thanks to recent advancements in therapy, treatment is very effective in managing the types of glycogen storage disease that affect the liver. GSD type I was considered a fatal disorder until 1971, when it was discovered that providing a continuous source of glucose ameliorated the metabolic derangements associated with the disorder. In 1982, uncooked cornstarch began to be used as a continuous glucose source, and the prognosis for patients living with this disorder improved dramatically. People with these types can now live full, normal lives.
GSDs that are not treated properly can lead to problems such as liver failure, heart failure, and lung failure. Quality of life and expected length of life are decreased in these cases. Because they affect so many organ systems, GSD Type II (Pompe’s disease) and GSD Type IV (Andersen’s disease) are very hard to treat and can be fatal.
Research into enzyme replacement therapy and gene therapy is promising, which may improve the outlook for the future.
When should I call my healthcare provider about GSD?
Call your healthcare provider if you have unexplained muscle weakness or any symptoms of low blood glucose, such as sweating, tremor, drowsiness and confusion.