Glycogen Storage Diseases
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Glycogen Storage Diseases

(Glycogenoses; GSD)

En Español (Spanish Version)

Definition

Glycogen storage diseases (GSDs) are a group of inherited genetic disorders that cause glycogen to be improperly formed or released in the body. They are characterized by the accumulation of abnormal amounts or types of glycogen in tissues.

Glycogen is the storage form of glucose in our bodies. Glucose is a simple sugar, which is a form of carbohydrate. It is found in many foods and is the main source of energy for our bodies.

The main types of GSDs are categorized by number and name. They include:

  • Type I (Von Gierke disease, defect in glucose-6-phosphatase)—This is the most common type of GSD and accounts for 90% of all GSD 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 glycogen phosphorylase deficiency)
  • Type VI (Hers’ disease, liver phosphorylase deficiency)
  • Type VII (Tarui’s disease, muscle phosphofructokinase deficiency)
  • Type IX (liver glycogen phosphorylase kinase deficiency)

Since glycogen is primarily stored in the liver or muscle tissue, GSDs usually affect functioning of the liver, the muscles, or both.

  • Liver—The GSDs that mainly affect the liver are types I, III, IV, VI, and IX.
  • Muscles—The GSDs that mainly affect muscles are types V and VII.
  • Type II affects nearly all organs including the heart.

Causes

GSDs occur when a genetic enzyme defect is inherited from both parents. Normally, enzymes help convert glucose into glycogen for storage. Other enzymes convert the glycogen back to glucose when quick energy is needed, as in exercise. In a person with a GSD, some of these enzymes are defective, deficient, or absent. This causes the build-up of abnormal amounts and types of glycogen in liver and/or muscle tissues.

Risk Factors

A risk factor is something that increases your chance of getting a disease or condition. The primary risk factor for GSDs is having a family member with this disease. The nature of that risk varies with the type of GSD because there are somewhat different types of inheritance among the different GSDs. Parents with one child with GSD typically have a 25% risk with each subsequent child. However, in a few of the GSD types, the risk rises to 50%, but only male children are affected.

Symptoms

The most common symptoms of GSDs include:

  • Low blood sugar
  • Enlarged liver
  • Slow growth
  • Muscle cramps

Signs and symptoms of specific types of GSDs include:

Type I:

  • Large and fatty liver and kidneys
  • Low blood sugar
  • High levels of lactate, fats, and uric acid in the blood
  • Impaired growth and delayed puberty
  • Osteoporosis
  • Increased mouth ulcers and infection

Type II:

  • Enlarged liver and heart
  • In severe cases, muscle weakness and heart problems develop.
  • In severe cases, infants may suffer fatal heart failure by the age of 18 months.
  • Milder forms of type II may not cause heart problems.

Enlarged Liver

enlarged liver

© 2008 Nucleus Medical Art, Inc.

Type III:

  • Swollen abdomen due to an enlarged liver
  • Growth delay during childhood
  • Low blood sugar
  • Elevated fat levels in blood
  • Possible muscle weakness

Type IV:

  • Growth delay in childhood
  • Enlarged liver
  • Progressive cirrhosis of the liver (which may lead to liver failure)
  • May affect muscles and heart in late-onset type

Type V:

  • Muscle cramps during exercise
  • Extreme fatigue after exercise
  • Burgundy-colored urine after exercise

Type VI, IX:

  • Liver enlargement occurs, but diminishes with age
  • Low blood sugar

Type VII:

  • Muscle cramps with exercise
  • Anemia

Diagnosis

The doctor will ask about symptoms and medical history and perform a physical exam. Diagnosis of GSDs usually occurs in infancy or childhood as a result of the above symptoms. Tests may include:

  • Biopsy of the affected organs
  • Blood and urine samples
  • MRI scan —a test that uses magnetic waves to make pictures of the inside of the body

When suspected early (generally because another child with GSD has been born to a set of parents), some types of GSD can be diagnosed using a technique called “pre-implantation genetic diagnosis.”

In this technique, based on procedures used for infertile couples, eggs and sperm are harvested from a couple who have a known risk for GSD, fertilized in the laboratory, and then an embryo (from those parents) shown to be free of GSD is implanted within the mother’s uterus. This technique allows parents to have additional unaffected children without resorting to abortion of an affected fetus. This use of GSD may still pose ethical or religious concerns for some couples.

Treatment

Treatment will depend on the type of GSD and the symptoms.

Treatment of GSDs That Affect the Liver

These general treatment guidelines apply to people with types I, III, IV, VI, and IX. Your doctor will develop a treatment regimen based on your specific symptoms.

The goal of treatment is to maintain normal blood glucose levels. This may be done with:

  • A nasogastric infusion of glucose in infants and children under age two.
  • Dietary changes, including:
    • In children over age two, frequent small carbohydrate feedings are given throughout the day. This may include uncooked cornstarch. (Uncooked cornstarch provides a steady slow-release form of glucose.)
    • Elimination of foods that are high in fructose or lactose (type I only).
  • Allopurinol (Aloprim, Zyloprim) may be prescribed to reduce uric acid levels in the blood. This is done to prevent gout and kidney stones .
  • Type IV is sometimes treated with liver transplantation .

Treatment of GSDs That Affect the Muscles

These general treatment guidelines apply to people with types V and VII. Your doctor will develop a treatment regimen based on your specific symptoms.

The goal of treatment is to avoid muscle fatigue and/or cramps induced by exercise. This is done by:

  • Regulating or limiting strenuous exercise to avoid fatigue symptoms
  • Improving exercise tolerance by oral intake of glucose or fructose (fructose must be avoided in people with type I), or an injection of glucagon
  • Eating a high protein diet

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 when deciding to have 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/cihiweb/dispPage.jsp?cw_page=home_e

References:

Harrison’s Principles of Internal Medicine . 14th ed. New York, McGraw-Hill; 1998.

Merck Manual of Diagnosis & Therapy . 17th ed. Simon and Schuster; 1999.



Last reviewed February 2008 by Jill D. Landis, MD

Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.

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