Your Health

Glycogen Storage Diseases

(Glycogenoses; GSD)

Definition

Glucose is a simple sugar. It is a form of carbohydrate. It is the main source of energy for our bodies. Glycogen is the storage form of glucose in our bodies.
Glycogen storage diseases (GSDs) are a group of inherited genetic disorders. They cause glycogen to be improperly formed or released in the body. This results in a build up of abnormal amounts or types of glycogen in tissues.
The main types of GSDs include:
  • Type 0, Liver glycogen synthase deficiency
  • Type I, Von Gierke disease, defect in glucose-6-phosphatase enzyme, the most common type of GSD accounting for 25% of all cases
  • Type II , Pompe’s disease, acid maltase deficiency
  • Type III, Cori’s disease, debrancher enzyme deficiency
  • Type IV, Andersen’s disease, brancher enzyme deficiency
  • Type V, McArdle’s disease, muscle phosphorylase deficiency
  • Type VI, Hers’ disease, liver phosphorylase deficiency
  • Type VII, Tarui’s disease, muscle phosphofructokinase deficiency
  • Type IX, phosphorylase kinase deficiency
Glycogen is mainly stored in the liver or muscle tissue. As a result, GSDs usually affect functioning of the liver, the muscles, or both.

Causes

GSDs are caused by a genetic enzyme defect. It is inherited from one or both parents.
Normally, enzymes help convert glucose into glycogen for storage. Other enzymes convert the glycogen back to glucose when energy is needed. This happens during activity like exercise. With GSD, some of these enzymes are defective, deficient, or absent.
The abnormal glycogen builds up in the liver and/or muscle tissues.

Risk Factors

The main risk factor for GSDs is having a family member with this disease. The risk varies with the type of GSD.

Symptoms

Each type of GSD has specific symptoms.

Type 0:

Type 0 symptoms commonly appear in late infancy when night feedings stop. In the early morning the child may low blood sugar which could cause:
  • Paleness
  • Vomiting
  • Extreme fatigue
  • Convulsions
The children may also have a mild growth delay. They also may have poor exercise tolerance.

Type I:

Type I may appear as early as 3 months old. Common symptoms include:
  • Protruding abdomen from an enlarged liver and seizures from low blood sugar are common in infants
  • Signs of low blood sugar including
    • Paleness
    • Irritability
    • Fatigue
    • Seizures
  • Growth delay
Enlarged Liver
enlarged liver
Copyright © Nucleus Medical Media, Inc.

Type II:

Type II is broken into the time of symptom onset. Infants generally show symptoms at 4-8 months of age. Type II can also form in childhood, adolescence, or adulthood.
Infant-onset Type II GSD symptoms include:
  • Muscle weakness and floppiness
  • Delayed motor skills
  • Weak breathing
  • Progressive heart muscle enlargement and reduced pumping may lead to fatal heart failure within first year of life
Late-onset Type II GSD symptoms include:
  • Progressive muscle weakness that spreads from the legs into the arms
  • Difficulty breathing

Type III:

Type III may appear in childhood. Common symptoms include:
  • Muscle weakness
  • Growth delay during childhood
  • Swollen abdomen due to an enlarged liver
  • Signs of low blood sugar including
    • Paleness
    • Irritability
    • Fatigue

Type IV:

Type IV appears during infancy. Common symptoms include:
  • Physical and mental development stops at a certain point and does not continue as normal
  • Progressive muscle weakness
  • Poor muscle development
  • Progressive cirrhosis of the liver, which may lead to liver failure

Type V:

Common symptoms of Type V include:
  • Muscle cramps during exercise
  • Extreme muscle fatigue during exercise
  • Potential fainting or seizure after exercise
  • Red or brown-colored urine after exercise

Type VI, IX:

Symptoms may not appear in people with Types VI or XI. When they do occur, symptoms include:
  • Enlarged liver in infancy
  • Mild growth delay
  • Anxiety, sweating, confusion, or seizures associated with low blood sugar

Type VII:

Common symptoms of Type VII include:
  • Muscle cramps and tenderness with exercise
  • Muscle fatigue with exercise
  • Red or brown-colored urine after exercise

Diagnosis

The doctor will ask about symptoms and medical history. A physical exam will be done. Diagnosis of GSDs usually occurs in infancy or childhood. It is often done by the symptoms listed above. Tests may include:
  • Biopsy of the affected organs
  • Blood and urine samples
  • MRI to see internal body structures
  • Genetic testing

Pre-implantation Genetic Diagnosis

This test may be used for an early diagnosis on some types of GSD. It is often done when there is a family history.
In this technique eggs and sperm are harvested from a couple who have a known risk. The egg is fertilized in the lab. The GSD free embryo is then implanted within the mother’s uterus. This technique allows parents to have additional unaffected children. This process may still pose ethical or religious concerns for some couples.
This test may be used for an early diagnosis on some types of GSD. It is often done when there is a family history.
In this technique eggs and sperm are harvested from a couple who have a known risk. The egg is fertilized in the lab. The GSD free embryo is then implanted within the mother’s uterus. This technique allows parents to have additional unaffected children. This process may still pose ethical or religious concerns for some couples.

Treatment

Treatment will depend on the type of GSD and the symptoms. Your doctor will develop a plan based on your specific symptoms.

Type 0

People with Type 0 need to manage their blood sugar throughout the day. This means frequent meals or snacks every few hours. Uncooked cornstarch provides a steady, slow release of glucose and may help prevent low blood sugar in the overnight hours. Other considerationfs includes eating a high amounts of protein.

Type I

Treatment for Type I includes eating small, frequent meals throughout the day. People with Type I may have to restrict certain sugars. This may include sugar found in fruits, juice, and candy. Eating uncooked cornstarch is also necessary. Many people will need to take a multivitamin.
Medications and procedure may be needed to control complications of Type 1 GSD.

Type II

Type II is treated with enzyme replacement therapy. Alglucosidase alpha is given by IV infusion.

Type III

People with Type III need to manage their blood sugar throughout the day. This means frequent meals or snacks every few hours. Diet for Type III includes high amounts of carbohydrates and cornstarch. Those with weak muscle involvment are generally put on a diet with high protein intake.
Liver transplant surgery may be necessary for some people who develop liver cancer or have liver failure.

Type IV

Type IV treatment focuses on treating progressive liver disease and its complications. Ultimately, a liver transplant may be necessary to survive. This does not improve damage to the muscles from the condition though.

Type V

There is no specific treatment for people with Type V GSD. Changing exercise patterns and avoiding certain activities may be important to help mangage this condition. Exercice tolerance may be improved by ingestion of some sugars prior to starting exercise.

Type VI and Type IX

Treatment includes cornstarch to avoid low blood sugars and eating adequate amounts of protein. Frequent meals may also be needed to help avoid low blood sugars. These changes can help promote normal growth and development.

Type VII

Type VII treatment focuses on avoiding high muscle stress. This can be accomplished by reducing strenous exercise to manageable levels. In some people, high protein intake has helped with muscle weakness.

Prevention

There is no way to prevent GSDs. However, early treatment can help control the disease once a person has it. If you have a GSD or a family history of the disorder, you may want to consult a genetic counselor. They can help determine the risk for your children.

RESOURCES

Association for Glycogen Storage Disease http://www.agsdus.org

Genetic Alliance http://www.geneticalliance.org

CANADIAN RESOURCES

Canadian Health Network http://www.canadian-health-network.ca

Canadian Institute for Health Information http://www.cihi.ca

References

Glycogen storage diseases. EBSCO DynaMed website. Available at: http://www.ebscohost.com/dynamed/what.php . Accessed June 6, 2013.

Glycogen and glycogen storage diseases. The Association for Glycogen Storage Disease website. Available at: http://www.agsdus.org/html/glycogenandgsds.html . Accessed June 6, 2013.

Hypoglycemia. National Diabetes Information Clearinghouse website Available at: http://diabetes.niddk.nih.gov/dm/pubs/hypoglycemia . Updated November 6, 2012. Accessed June 6, 2013.

5/28/2010 DynaMed's Systematic Literature Surveillance http://www.ebscohost.com/dynamed/what.php : FDA approves new treatment for late-onset Pompe disease. US Food and Drug Administration website. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm213282.htm . Published May 25, 2010. Accessed June 6, 2013.

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