$Unique_ID{BRK03747} $Pretitle{} $Title{Forbes Disease} $Subject{Forbes Disease Amylo-1,6-Glucosidase Deficiency Cori Disease Debrancher Deficiency Glycogen Storage Disease III Glycogenosis Type III Limit Dextrinosis Von Gierke Disease Andersen Disease Hers Disease Glycogen Storage Disease VIII} $Volume{} $Log{} Copyright (C) 1987, 1990, 1991 National Organization for Rare Disorders, Inc. 396: Forbes Disease ** IMPORTANT ** It is possible the main title of the article (Forbes 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 Amylo-1,6-Glucosidase Deficiency Cori Disease Debrancher Deficiency Glycogen Storage Disease III Glycogenosis Type III Limit Dextrinosis Information on the following diseases can be found in the Related Disorders section of this report: Von Gierke 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. Forbes Disease is a glycogen storage disorder inherited through autosomal recessive genes. Symptoms are caused by a lack of the enzyme amylo-1,6 glucosidase (debrancher enzyme). This enzyme deficiency causes excess amounts of glycogen (the stored form of energy that comes from carbohydrates) to be deposited in the liver, muscles and heart. The heart may be involved in some cases. Symptoms Symptoms of Forbes Disease during the first 4 to 6 years of life may be indistinguishable from Von Gierke Disease. The amounts of glycogen in the liver and muscles is abnormally high. The liver is enlarged and the abdomen protrudes. The muscles tend to be flaccid. A child with Forbes Disease has a short stature, low blood sugar (hypoglycemia) that does not respond to the hormone glucagon, and an elevated level of fatty substances in the blood, known as hyperlipemia. Patients with Forbes Disease may also have difficulty fighting infections, and may experience unusually frequent nosebleeds. Some individuals may have virtually no other symptoms of Forbes Disease other than a protruding abdomen and an enlarged liver. These patients tend to lose these few symptoms during adolescence when their liver decreases progressively in size. Children with Forbes Disease often grow slowly during childhood and puberty may be delayed, but their adult height is usually normal. Causes Forbes Disease is a disorder inherited through autosomal recessive genes. The disorder is caused by lack of a debrancher enzyme (amylo-1,6-glucosidase) which is involved in the formation of the stored form of carbohydrates (glycogen). Glycogen is stored in the liver and muscles for future energy needs when it is converted into sugar (glucose). Glucose is used as a readily available source of energy. Without the debrancher enzyme, glycogen can only be broken down partially and the structure that is left, resembling a molecule called a "limit dextrin", may accumulate in liver and muscle 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 All Glycogen Storage Diseases together affect less than 1 in 40,000 persons in the United States. Forbes Disease usually begins during childhood. It affects males as often as females. Patients with this disorder reported in Israel were generally of North African heritage. Related Disorders Glycogen Storage Diseases involve 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 Forbes Disease. These can be compared with Forbes Disease for a differential diagnosis: Von Gierke Disease is a more severe form of glycogen storage disease. It is a hereditary metabolic disorder caused by an inborn lack of either the enzyme glucose-6-phosphatase or the enzyme glucose-6-phosphate translocase. These enzymes are needed to convert the main carbohydrate storage material (glycogen) into sugar (glucose) which the body uses for its energy needs. A deficiency of these enzymes causes abnormal deposits of glycogen in the liver and kidney cells. 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 are 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 "Von Gierke," "Andersen," "Hers," and "Glycogen Storage VIII" as your search terms in the Rare Disease Database. Therapies: Standard Diagnosis of Forbes Disease may be confirmed by tests for the presence of glycogen and the debrancher enzyme in muscle and liver biopsies. White blood cells and connective tissue cells called fibroblasts can also be useful for similar diagnostic tests. Treatment of Forbes Disease is aimed at prevention of low blood sugar (hypoglycemia). Frequent small servings of carbohydrates and a high protein diet are advised during the day. At night continuous tube feeding of food solutions such as Vivonex or polycose (glucose) may be administered to promote normal childhood growth. Genetic counseling is helpful for families of children with Forbes Disease and other Glycogen Storage Diseases. People with this disorder can expect to live a normal life span. However, muscle disorders may develop with age. Therapies: Investigational 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 February 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 Forbes 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 MYOPATHY AND GROWTH FAILURE IN DEBRANCHER ENZYME DEFICIENCY: IMPROVEMENT WITH HIGH-PROTEIN NOCTURNAL ENTERAL THERAPY: A.E. Slonim, et al.; Journal of Pediatrics (December 1984: issue 105,6). Pp. 906-911. NEUROMUSCULAR INVOLVEMENT IN GLYCOGEN STORAGE DISEASE TYPE III: S.W. Moses, et al.; Acta Paediatrica Scandinavica (March 1986: issue 75,2). Pp. 289-296.