Forbes Disease

Forbes Disease

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Forbes Disease is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Amylo-1,6-Glucosidase Deficiency
  • Cori Disease
  • Debrancher Deficiency
  • Glycogen Storage Disease III
  • Glycogenosis Type III
  • Limit Dextrinosis

Disorder Subdivisions

  • None

General Discussion

Forbes disease (GSD-III) is one of several glycogen storage disorders (GSD) that are inherited as autosomal recessive traits. Symptoms are caused by a lack of the enzyme amylo-1,6 glucosidase (debrancher enzyme). This enzyme deficiency causes excess amounts of an abnormal glycogen (the stored form of energy that comes from carbohydrates) to be deposited in the liver, muscles and, in some cases, the heart.



There are two forms of this disorder. GSD-IIIA affects about 85% of patients with Forbes disease and involves both the liver and the muscles. GSD-IIIB affects only the liver.

Symptoms

Symptoms of Forbes disease, at least during the first 4 to 6 years of life, may be indistinguishable from another of the glycogen storage diseases, Von Gierke disease. The amount of glycogen in the liver and muscles is abnormally high and, because the liver is enlarged (hepatomegaly), 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 other individuals may have virtually no symptoms (asymptomatic) 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

The defective gene responsible for GSD-III has been traced to Gene Map Locus 1p21, and the disorder is transmitted as an autosomal recessive trait. It 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", accumulates 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 for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.



All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Affected Populations

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.

Standard Therapies

Diagnosis

The presence of Forbes disease is definitive if testing liver and muscle tissues (biopsies) for abnormal glycogen and debrancher enzyme is positive. White blood cells and connective tissue cells called fibroblasts can also be useful as a screen, but may not provide a definitive diagnosis.



Treatment

Forbes disease is treated by continuous glucose delivery (intravenous drip) in order to avoid 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 polyglucose (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.

Investigational Therapies

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.



Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

Weinstein DA, Koeberl DD, Wolfsdorf JI. Type III Glycogen Storage Disease. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:453.



Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:2387-89.



Berkow R., ed. The Merck Manual-Home Edition. Whitehouse Station, NJ: Merck Research Laboratories; 1997:1291-92.



Chen YT, Burchell A. Glycogen Storage Diseases. In: Scriver CR, Beaudet AL, Sly WS, et al. Eds. The Metabolic Molecular Basis of Inherited Disease. 7th ed. McGraw-Hill Companies. New York, NY; 1995:935-65.



Greene HL. Glycogen Storage Diseases. In: Bennett JC, Plum F. Eds. Cecil Textbook of Medicine. 20th ed. W.B. Saunders Co., Philadelphia, PA; 1996:1082-83.



REVIEW ARTICLES

Shen JJ, Chen YT. Molecular characterization of glycogen storage disease type III. Curr Mol Med. 2002;2:167-75.



Matern D, Starzl TE, Arnaout W, et al. Liver transplantation for glycogen storage disease types I, III, and IV. Eur J Pediatr. 1999;158 Suppl 2:S43-48.



JOURNAL ARTICLES

Lucchiari S, Donati MA, Parini R, et al. Molecular characterization and identification of six novel mutations in AGL. Hum Mutat. 2002;20:480.



OKI Y, Okubo M, Tanaka S, et al. Diabetes mellitus secondary to glycogen storage disease type III. Diabet Med. 2000;17:810-12.



Hershkovitz E, Donald A, Mullen M, et al. Blood lipids and endothelial function in glycogen storage disease type III. J Inherit Metab Dis. 1999;22:891-98.



Kiechl S, Willen J, Vogel W, et al. Reversible severe myopathy of respiratory muscles due to adult-onset type III glycogenosis. Neuromuscul Dis. 1999;9:408-10.



Kiechl S, Kohlendorfer U, Thaler C, et al. Different clinical aspects of debrancher deficiency myopathy. J Neurol Neurosurg Psychiatry. 1999;67:364-68.



Shen J, Liu HM, McConkie-Rosell A, et al. Prenatal diagnosis and carrier detection for glycogen storage disease type III using polymorphic DNA markers. Prenat Diagn. 1998;18:61-64.



FROM THE INTERNET

McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Entry Number; 232400: Last Edit Date; 6/4/2002.



Sloan HR. Glycogen Storage Disease Type III. eMedicine. Last Updated; January 17, 2003. 23pp.

www.emedicine.com/ped/topic479.htm



Anderson WE. Glycogen Storage Disease Type III. eMedicine. Last Updated; December 27, 2001. 8pp.

www.wmedicine.com/med/topic909.htm



Glycogen Storage Disease Type III. Last Modified;11 Feb 1996. 2pp.

http://oxmedinfo.jr2.ox.ca.uk/Pathway/Disease/83994.htm



Glycogen Storage Disease Laboratory, Duke University Medical Center. Glycogen Storage Disease Type III. Dated; 17 Oct. 2001. 1p.

www.duke.edu/~mdfeezor/dukemedicalgenetics/gsdiii.htm

Resources

CLIMB (Children Living with Inherited Metabolic Diseases)

Climb Building

176 Nantwich Road

Crewe, CW2 6BG

United Kingdom

Tel: 4408452412173

Fax: 4408452412174

Email: enquiries@climb.org.uk

Internet: http://www.CLIMB.org.uk



Association for Glycogen Storage Disease

P.O. Box 896

Durant, IA 52747

USA

Tel: (563)514-4022

Fax: (563)514-4022

Email: info@agsdus.org

Internet: http://www.agsdus.org



Muscular Dystrophy Association

3300 East Sunrise Drive

Tucson, AZ 85718-3208

USA

Tel: (520)529-2000

Fax: (520)529-5300

Tel: (800)572-1717

Email: mda@mdausa.org

Internet: http://www.mda.org/



Association for Glycogen Storage Disease (UK) Ltd

Old Hambledon Racecourse

Sheardley Lane, Droxford

Hampshire, SO32 3QY

United Kingdom

Tel: 03001232790

Email: info@agsd.org.uk

Internet: http://www.agsd.org.uk



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



For a Complete Report

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