Glycogen storage diseases: What are the differences?

Glycogen storage disease (GSD) is a rare genetic condition in which the body is not able to store or break down glycogen (a complex sugar) properly. GSDs can have different forms and subtypes, and by some accounts, there are more than 13 different types of GSD. Below, we break down the key differences between a few of the most common types of GSD. 

The basics of glycogen storage disease

In order to function properly, your body’s cells need a steady supply of fuel in the form of a simple sugar called glucose, which comes from breaking down the food we eat. Your body uses as much glucose as it needs to function normally and stores the rest for later.

Before it’s stored for later use, the body must combine the glucose units into glycogen, a complex sugar. Glycogen is stored in the liver and muscle cells, and when your body needs more fuel, it breaks down the glycogen stored in the liver back into glucose units cells can use. Enzymes typically help make and break down glycogen in a process called glycogen metabolism, but sometimes, a person is born missing an enzyme needed for this process. This causes the body to have trouble storing or breaking down the glycogen as it should, leading to very low blood glucose levels during periods of fasting. Muscles and organs need a certain level of glucose in the blood to work properly.

GSD is when the body is missing an enzyme (or has a flawed enzyme system) and is not able to use glycogen correctly. Since there are many different enzymes used to process glycogen, there are several types of GSD.

Key differences between different types of glycogen storage disease

The overall GSD incidence is estimated at 1 case per 20,000-43,000 live births. The most common types of GSD are types I, II, III, and IV, with GSD I being the most prevalent.

• GSD I (also known as von Gierke disease): This is by far the most common form of GSD. People with GSD I don’t have the enzyme needed to turn glycogen into glucose in the liver. Symptoms can appear in babies as young as 3 to 4 months old and may include low blood sugar and a swollen stomach because of an enlarged liver. GSD I has two main types, GSD Ia and GSD Ib. GSD Ia is caused by a deficiency in the enzyme glucose-6-phosphatase, and GSD Ib is caused by a deficiency in the enzyme glucose-6-phosphate translocase.
• GSD II (also known as Pompe disease): GSD II is a disorder that damages muscle and nerve cells throughout the body. It is caused by an accumulation of glycogen in the lysosome (a membrane-bound cell organelle that contains digestive enzymes) due to deficiency of the lysosomal acid alpha-glucosidase enzyme. It is the only glycogen storage disease with a defect in lysosomal metabolism The build-up of glycogen causes progressive muscle weakness throughout the body and can affect various body tissues, particularly in the heart, skeletal muscles, liver, and the nervous system.
• GSD III (also known as Forbes disease or Cori disease): People with GSD III don’t have enough of the debranching enzyme, which helps break down glycogen, causing it to collect in the liver and in muscle tissues. Symptoms include a swollen abdomen , delayed growth, low blood sugar, and muscle weakness.
• GSD IV (also known as Andersen disease): GSD IV causes the body to form abnormal glycogen. Experts believe the abnormal glycogen triggers the immune system, which creates scarring of the liver, muscles, the heart, and skin.
• GSD V (also known as McArdle disease): GSD V is an ultra-rare glycogen disorder and can cause exhaustion, cramping, and muscle pain in everyday activities. People with GSD V typically experience fatigue, muscle pain, and cramps during the first few minutes of exercise. 

Most of the severe forms of GSD are diagnosed in babies and children. Because of mild symptoms, GSD might also be underdiagnosed, and might not be found until the person is an adult. 

Treatment varies depending on the type of GSD. One thing is certain, though: research can’t move forward without GSD clinical trial participants. Do you have GSD III? Learn more about participating in a study by clicking the link below.