Glycogen Storage Disease (GSD)

Glycogen storage disease (GSD) is a rare metabolic disorder where the body is not able to properly store or break down glycogen, a form of sugar or glucose. GSD affects the liver, muscles and other areas of the body, depending on the specific type.

The body’s cells need a steady supply of fuel, in the form of a simple sugar called glucose to function. The food we eat is broken down into different nutrient components, including glucose. The excess glucose that is not needed right away is stored as glycogen in the liver and muscle cells to use later. When the body needs more energy, enzymes break down glycogen into glucose, a process called glycogen metabolism or glycogenolysis.

Children with GSD are missing one of the several enzymes that break down glycogen, and glycogen can build up in the liver, causing problems in the liver, muscles or other parts of the body. When the enzyme deficiency affects the liver, it leads to low blood glucose levels (also called hypoglycemia) during periods of fasting (between meals or at night).

GSD is hereditary, meaning it is passed down from parents to children. For most types of GSD, both parents are unaffected carriers, meaning they carry one copy of a misspelled gene that can cause GSD paired with a normal copy of the gene. When both parents pass the misspelled gene to a child, the child has no normal copy of that gene and therefore develops GSD. In most cases GSD is diagnosed within the first year of life, but in some cases the diagnosis may not be made until later in childhood.

Glycogen storage disorders occur in about one in 20,000 to 25,000 newborn babies.

Many different enzymes are used by the body to process glycogen. As a result, there are several types of GSD.

One type of glycogen storage disease, Type II (Pompe’s disease), is part of the newborn screening panel in many states. This type of GSD does not cause hypoglycemia. If it is detected in the child’s blood, the child will be referred to a pediatric hospital like Children’s Hospital of Philadelphia that has expertise caring for babies with rare conditions.

Manifestations of GSD often look like other health problems and may include:

• poor growth
• low blood glucose level (hypoglycemia)
• an enlarged liver (may show as a bulging abdomen)
• abnormal blood tests
• low muscle tone
• muscle pain and cramping during exercise
• too much acid in the blood (acidosis)
• fatigue

A thorough medical history can also lead the doctor to suspect GSD since it is inherited. Other diagnostic tests may include:

• blood tests to check blood glucose levels and how the liver, kidneys and muscles are functioning
• abdominal ultrasound to see if the liver is enlarged
• tissue biopsy to test a sample of tissue from muscle or liver to measure the level of glycogen or enzymes
• genetic testing, which can confirm a GSD

Each type of GSD centers on a certain enzyme or set of enzymes involved in glycogen storage or break down. GSD mostly affects the liver and the muscles, but some types cause problems in other areas of the body as well. Types of GSD (with their alternative names) and the parts of the body they affect 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 (phosphorylase kinase deficiency) – liver
• type XI (Fanconi-Bickel syndrome) – liver, kidneys, intestines

The most common types of GSD are types I, II, III and IV, accounting for nearly 90% of all cases. About 25% of patients with GSD are thought to have type I. GSD types VI and IX can have very mild symptoms and may be underdiagnosed or not diagnosed until adulthood.

Currently, there is no cure for GSD. Treatment will vary depending on what type of GSD your child has; however, the overall goal is to maintain the proper level of glucose in the blood so cells have the fuel they need to prevent long-term complications.

At Children’s Hospital of Philadelphia, children with types 0, Ia, Ib, III, VI and IX are seen in a special Glycogen Storage Disease Clinic within the Division of Endocrinology and Diabetes, as these children will have low blood sugar that needs to be managed. Children with other types are seen in CHOP’s Lysosomal Storage Disease Center, which is within the Metabolic Disease Program.

Until the early 1980s, children with GSDs had few treatment options and none were very helpful. Then it was discovered that ingesting uncooked cornstarch regularly throughout the day helped these children maintain a steady, safe glucose level. Cornstarch is a complex carbohydrate that is difficult for the body to digest; therefore it acts as a slow release carbohydrate and maintains normal blood glucose levels for a longer period of time than most carbohydrates in food.

Cornstarch therapy is combined with frequent meals (eating every two to four hours) of a diet that restricts sucrose (table sugar), fructose (sugar found in fruits) and lactose (only for those with GSD I). Typically, this means no fruit, juice, milk or sweets (cookies, cakes, candy, ice cream, etc.) because these sugars end up as glycogen trapped in the liver. Infants need to be fed every two hours. Those who are not breastfed must take lactose-free formula.

Some types of GSD require a high-protein diet. Calcium, vitamin D and iron supplements maybe recommended to avoid deficits.

Children need their blood glucose tested frequently throughout the day to make sure they are not hypoglycemic, which can be dangerous. Some children, especially infants, may require overnight feeds to maintain safe blood glucose levels. For these children, a gastrostomy tube, often called a g-tube, is placed in the stomach to make overnight feedings via a continuous pump easier.

Children may be prescribed medicines to manage side effects of GSD. These include:

• Allopurinol, a drug capable of reducing the level of uric acid in the blood, may be useful to control the symptoms of gout-like arthritis during the adolescent years in patients with GSD I.
• Medications may be prescribed to lower lipid levels and prevent and/or treat kidney disease.
• Human granulocyte colony stimulating factor (GCSF) may be used to treat recurrent infections in GSD type Ib patients.

In certain types of GSD, children must limit their amount of exercise to reduce muscle cramps.

The outlook depends on the type of GSD and the organs affected. With recent advancements in therapy, treatment is effective in managing the types of glycogen storage disease that affect the liver.

Children may have an enlarged liver, but as they grow and the liver has more room, their prominent abdomen will be less noticeable.

Other complications include benign (noncancerous) tumors in the liver, scarring (cirrhosis) of the liver and, if lipid levels remain high, the formation of fatty skin growths called xanthomas.

To manage complications, children with GSD should been seen by a doctor who understands GSDs every three to six months. Blood work is needed every six months. Once a year, they need a kidney and liver ultrasound.

Genetic counseling is recommended for affected individuals and their families.

Research into enzyme replacement therapy and gene therapy is promising and may improve the outlook for the future. CHOP will be a site for upcoming gene therapy clinical trials for types I and III. The GSD Clinic will have more information.