Glycogen Storage Disease

Glycogen storage disease (GSD) is the name for a group of disorders that interfere with the body’s ability to make glycogen or convert glycogen into glucose. Depending on the type of GSD a child has, glycogen may build up in the liver, in the muscles, or both. GSD can also affect blood cells, the heart, kidneys, and other organs.

Glycogen is the body’s primary source of energy. Normally, glycogen is stored in the liver until the body needs energy. Then, enzymes convert glycogen into glucose so that it can travel through the bloodstream to cells that need fuel. Every cell in the body contains enzymes, but children with GSD lack one of the enzymes responsible for making glycogen or converting glycogen to glucose.

GSD is a rare condition. According to the National Organization of Rare Diseases, GSD affects fewer than 1 in 40,000 people in the United States.

There are many different types of GSD, based on which enzyme is missing. Some types affect only the liver, others only the muscles, while some affect both the liver and the muscles. Each type has slightly different symptoms. Treatments vary for the various types of GSD.

The most common types of GSD include:

Glycogen storage disease type I (GSD I), also known as von Gierke disease, accounts for about 25 percent of all children with GSD. Symptoms typically appear when an infant is 3 to 4 months of age and may include hypoglycemia (low blood sugar), which can cause fatigue, constant hunger, and crankiness. The liver and sometimes the kidneys swell due to built-up glycogen.

Glycogen storage disease type III (GSD III), also known as Cori disease or Forbes disease, causes glycogen to build up in the liver and muscles. Symptoms typically appear within the first year of life. Children with this type of GSD may have a swollen belly, delayed growth, and weak muscles.

Glycogen storage disease type IV (GSD IV), also known as Andersen disease, is one of the most serious types of GSD. Symptoms typically appear in a child’s first month of life and include failure to gain weight or grow at an expected rate. This type of GSD often leads to cirrhosis of the liver and can affect the heart and other organs as well. The child’s outcomes depend on the form of GSD IV they inherit.

Each type of GSD carries specific risks.

Infants with type I (GSD I) may have low blood sugar. This type of GSD can also lead to lactic acidosis, a buildup of lactic acid, which can cause painful muscle cramps. As they mature into adolescence, children with GSD I may have delayed puberty and weak bones (osteoporosis). Other risks include:

• Gout, a type of arthritis
• Adenomas, tumors of the liver that are usually benign (non-cancerous)
• Inflammatory bowel disease (type 1b)
• Dental problems
• Recurring infections (type 1b)
• Pulmonary hypertension

Infants with type III (GSD III) may have low blood sugar and excess fat in their blood. As they get older, their livers may become enlarged. Some children’s livers go back to a normal size when they hit adolescence, but others develop cirrhosis and liver failure. Children with this type of GSD are also at risk for:

• Slow growth and short stature
• Muscle weakness

Infants with Type IV (GSD IV) may not have low blood sugar, but they can develop early complications. Children who survive with GSD IV are at risk for the following complications:

• Slow weight gain
• Muscle weakness, including a weak heart muscle
• Cirrhosis
• Portal hypertension

Symptoms of GSD typically appear early, when a child is still a baby or very young child.

Though symptoms vary depending by type of GSD, the following symptoms are common:

• Delayed growth
• Easy bruising
• Swollen belly
• Weak muscles
• Muscle pain and cramping
• Chronic hunger
• Irritability

GSD is an inherited disease. Children are born with GSD when both parents have an abnormal gene that gets passed on to one of their children. Their parents typically don’t have the disease or any of its symptoms.

Children with GSD lack one of the enzymes responsible for making glycogen or converting glycogen to glucose. As a result, their muscles do not receive the fuel they need to grow and glycogen builds up in their liver and other organs.

Diagnosis starts with a health history. Your child’s doctor will ask about your child’s symptoms and overall health. The doctor will also do a physical exam and check for signs of an enlarged liver or weak muscles.

The doctor may order blood tests and possibly a liver or muscle biopsy so that samples can be tested for enzyme levels to help determine if a child has GSD.

There is currently no cure for GSD. After diagnosis, children with GSD are usually cared for by several specialists, including specialists in endocrinology and metabolism. Specific dietitians with expertise in this disease should be involved.

Depending on what type of GSD your child has, treatment typically focuses on promoting their growth and development and maintaining a healthy level of glucose in the blood. Typically, doctors recommend small, frequent meals throughout the day. The meals should be low in sugar to prevent glycogen from building up in the liver. Uncooked cornstarch can help maintain a healthy blood-sugar level.

In some cases, doctors may recommend a nasogastric tube or gastrostomy (G tube) that delivers a continuous supply of nutrition while the child is sleeping.

Children with GSD IV may need a liver transplant if the disease progresses to cirrhosis or liver failure.

The Center for Childhood Liver Disease at Boston Children’s Hospital specializes in helping infants, children, adolescents, and young adults with a wide variety of liver, gallbladder, and bile duct disorders (otherwise known as hepatobiliary). Doctors refer children with liver disease to our program at Boston Children’s from all over the world.