$Unique_ID{BRK04316} $Pretitle{} $Title{Von Gierke Disease} $Subject{Von Gierke Disease Glycogen Storage Disease I Glycogenosis Type I Hepatorenal Glycogenosis Glycogenosis Type IA Glucose-6-Phosphatase Deficiency Glycogenosis Type IB Glucose-6-Phosphate Translocase Deficiency Glucose-6-Phosphate Transport Defect Forbes Disease Andersen Disease Hers Disease Glycogen Storage Disease VIII } $Volume{} $Log{} Copyright (C) 1987, 1990, 1991 National Organization for Rare Disorders, Inc. 393: Von Gierke Disease ** IMPORTANT ** It is possible the main title of the article (Von Gierke Disease) is not the name you expected. Please check the SYNONYMS listing on the next page to find alternate names, disorder subdivisions, and related disorders covered by this article. Synonyms Glycogen Storage Disease I Glycogenosis Type I Hepatorenal Glycogenosis DISORDER SUBDIVISIONS: Glycogenosis Type IA, also known as Glucose-6-Phosphatase Deficiency Glycogenosis Type IB, also known as Glucose-6-Phosphate Translocase Deficiency, and Glucose-6-Phosphate Transport Defect Information on the following disorders can be found in the Related Disorders section of this report: Forbes Disease Andersen Disease Hers Disease Glycogen Storage Disease VIII General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Von Gierke Disease is a glycogen storage disease. This hereditary metabolic disorder is caused by an inborn lack of the enzyme glucose-6- phosphatase. This enzyme is needed to convert the main carbohydrate storage material (glycogen) into sugar (glucose) which the body uses for its energy needs. A deficiency causes deposits of excess glycogen in the liver and kidney cells. Symptoms Symptoms of Von Gierke Disease usually begin during the first year of life. The disorder is characterized by persistent hunger, fatigue and irritability. These symptoms are especially noticeable in infants. Other symptoms include marked enlargement of the liver (hepatomegaly), weight loss and a slow growth rate. If food is withheld, a low blood sugar level (hypoglycemia) and an abnormally high level of acetone, aceto-acetic acid and beta-hydroxybutyric acid (also called ketones) may develop in the blood and body tissues. This is called ketosis. If the hypoglycemia is severe, patients may experience seizures. Children with Von Gierke Disease may bruise easily and may experience frequent nosebleeds. An increased level of cholesterol and fatty acids in the blood (lipidemia) may lead to yellow lipid deposits under the skin (xanthoma) in the joint areas of the arms and legs. Small spaces (vacuoles) filled with the main carbohydrate storage material (glycogen) may be seen microscopically in liver cells and throughout the kidneys. An excess of uric acid in the blood (hyperuricemia) may also occur. The course of the disorder can be severe at times. However, the symptoms tend to improve gradually with age. Causes Von Gierke Disease is inherited through autosomal recessive genes. This disorder is caused by a lack of the enzyme glucose-6-phosphatase. A deficiency causes excess amounts of glycogen to be stored in the body's tissues. (Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits the same defective gene from each parent. If one receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will show no symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is twenty-five percent. Fifty percent of their children will be carriers, but healthy as described above. Twenty-five percent of their children will receive both normal genes, one from each parent and will be genetically normal.) Affected Population Von Gierke Disease and other glycogen storage disorders together affect about 1 in 40,000 persons in the United States. It affects males and females in equal numbers. Related Disorders Glycogen Storage Diseases are caused by inborn errors of metabolism in which the balance between stored energy (glycogen) and available energy (sugar or glucose) is disturbed. Too much glycogen tends to be stored in the liver and muscles and too little sugar is available in the blood. The following diseases are similar to Von Gierke Disease. Comparisons may be useful for a differential diagnosis: Forbes Disease (Glycogenosis III; Cori Disease) is another genetic glycogen storage disease. This disorder is caused by a lack of a debrancher (dextrin-1-6-glucosidase) enzyme. This enzyme deficiency causes excess amounts of glycogen to be deposited in the liver and muscles. The nerves in the back of the legs and on the sides of the heel and foot (sural nerves) also accumulate excess glycogen. The heart may be involved in some cases. Andersen Disease is a glycogen storage disease inherited through recessive genes. Symptoms of this disorder are caused by a lack of a brancher enzyme amylo transglucosidase. The lack of this enzyme causes an abnormality in the structure of the main carbohydrate storage material (glycogen). Andersen Disease is characterized by scarring of the liver (cirrhosis) which may lead to liver failure. Hers Disease is a mild genetic form of glycogen storage disease. The disorder is caused by a deficiency of the enzyme liver phosphorylase. Hers Disease is characterized by enlargement of the liver (hepatomegaly), moderately low blood sugar (hypoglycemia), elevated levels of acetone and other ketone bodies in the blood (ketosis), and moderate growth retardation. Symptoms are not always evident during childhood. Children may be able to lead normal lives. In other cases, severe symptoms may be present. Glycogen Storage Disease VIII is a sex-linked genetic disorder caused by a deficiency of the enzyme liver phosphorylase kinase. The disorder is characterized by slightly low blood sugar (hypoglycemia). Excess amounts of glycogen (the stored form of energy that comes from carbohydrates) are deposited in the liver, causing enlargement of the liver (hepatomegaly). For more information on the above disorders, choose "Forbes," "Anderson," "Hers," and "Glycogen Storage Disease VIII" as your search terms in the Rare Disease Database. Therapies: Standard Diagnosis of Von Gierke Disease may be confirmed by tests that measure the body's reaction to sugar when it is added to the blood stream (glucose test), a test that measures the body's reaction to glucagon (glucagon tolerance test). Treatment of Von Gierke Disease is aimed at prevention of low blood sugar (hypoglycemia) and ketosis through a carefully controlled diet. Frequent small servings of carbohydrates and a high protein diet during the day must be maintained throughout life. At night continuous tube feeding of food solutions such as Vivonex may be administered to promote normal childhood growth. The uric acid concentration in the blood must be carefully monitored to prevent gouty arthritis during adolescence or adulthood. 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. Recently the use of cornstarch as an overnight feeding, one cup of cornstarch before bed, has shown great promise. Not only does this procedure eliminate other forms of feeding throught the night, but it has improved blood levels of glucose and lowered amino acid asnd phosphate loss. It has been documented that this treatment has shown an increased growth of some patients and a decrease in damage to the kidney's proximal tubules. Genetic counseling can be helpful for families of children with Von Gierke Disease and other Glycogen Storage Diseases. Although the disorder is not curable it is treatable with appropriate medication, diet control and monitoring to prevent complications. Therapies: Investigational Dr. Yuan-Tsong Chen, M.D., Ph.D. of Duke University, Durham, NC, was awarded a grant in 1988 by the Orphan Products Division for his work using cornstarch as a treatment for Von Gierke Disease (Type I Glycogen Storage Disease). Dr. Y.T. Chen at Duke University Medical Center, at the request of the Glycogen Storage Disease Association, is collecting DNA from patients with Glycogen Storage Disease Type I to form a DNA bank for GSDI. Interested patients may contact the Glycogen Storage Diseases Association for further information. The address and phone number of the organization are listed in the Resources section of this report. This disease entry is based upon medical information available through May 1991. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Von Gierke Disease, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Association for Glycogen Storage Diseases Box 896 Durant, IA 52747 (319) 785-6038 National Digestive Diseases Information Clearinghouse Box NDDIC Bethesda, MD 20892 (301) 468-6344 Research Trust for Metabolic Diseases in Children Golden Gates Lodge, Weston Rd. Crewe CW1 1XN, England Telephone: (0270) 250244 For information on genetics and genetic counseling referrals, please contact: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References OPTIMAL RATE OF ENTERAL GLUCOSE ADMINISTRATION IN CHILDREN WITH GLYCOGEN STORAGE DISEASE TYPE I: W.F. Schwenk, et al.; New England Journal of Medicine (March 13, 1986: issue 314,11). Pp. 682-685. GLYCOGEN STORAGE DISEASE TYPE I. RESULTS OF TREATMENT WITH FREQUENT DAYTIME FEEDING, COMBINED WITH NOCTURNAL INTRAGASTRIC FEEDING AND WITH ADMINISTRATION OF AN ALPHA-GLUCOSIDASE INHIBITOR: H. Grube, et al.; European Journal of Pediatrics (April 1983: issue 140,2). Pp. 102-104.