Glycogen storage disease type 3

Title

Other Names:

Forbes disease; Cori disease; Limit dextrinosis; Forbes disease; Cori disease; Limit dextrinosis; Amylo-1,6-glucosidase deficiency; Glycogen debrancher deficiency See More

Categories:

Congenital and Genetic Diseases; Digestive Diseases; Heart Diseases; Congenital and Genetic Diseases; Digestive Diseases; Heart Diseases; Metabolic disorders; Nervous System Diseases See More

Summary Summary

Glycogen storage disease type 3 (GSDIII) is an inherited disorder caused by the buildup of glycogen in the body's cells. This buildup impairs the function of certain organs and tissues, especially the liver and muscles. Symptoms typically begin in infancy and may include hypoglycemia, hyperlipidemia (excess of fats in the blood), and elevated blood levels of liver enzymes; later symptoms may include hepatomegaly, chronic liver disease (cirrhosis) and liver failure later in life. Some individuals have short stature and noncancerous (benign) tumors called adenomas in the liver. GSDIII is cause by mutations in the AGL gene and is inherited in an autosomal recessive manner.^[1] Treatment typically includes a high-protein diet with cornstarch supplementation to maintain a normal level of glucose in the blood.^[2] GSDIII is divided into types IIIa, IIIb, IIIc, and IIId; types IIIa and IIIc mainly affect the liver and muscles, and GSD types IIIb and IIId typically affect only the liver.^[1]

Last updated: 2/13/2012

Symptoms Symptoms

In infancy, individuals with glycogen storage disease type 3 (GSDIII) may have low blood sugar (hypoglycemia), increased amounts of fats in the blood (hyperlipidemia), and elevated levels of liver enzymes in the blood.^[3] Hypoglycemia may cause occasional seizures in some individuals.^[4] As they age, children usually develop an enlarged liver (hepatomegaly), which can cause the abdomen to protrude. Liver size may return to normal during adolescence, but some affected individuals develop chronic liver disease and subsequent liver failure years later. Individuals often have delayed growth due to their liver problems, which can lead to short stature. They may also have difficulty fighting infections, and may experience unusually frequent nosebleeds. A small percentage of individuals develop benign (non-cancerous) tumors in the liver called adenomas.^[3]^[5]

GSD types IIIa and IIIc typically affect both the liver and muscles, while types IIIb and IIId typically affect only the liver. Individuals with type IIIa may develop myopathy in both the heart and skeletal muscles later in life. The first signs and symptoms of this are typically poor muscle tone (hypotonia) and mild myopathy in early childhood. The myopathy may become severe by early to mid-adulthood.^[3]

Last updated: 2/13/2012

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Full cheeks	Very frequent (present in 80%-99% of cases)
Hypertriglyceridemia	Very frequent (present in 80%-99% of cases)
Hypoglycemia	Very frequent (present in 80%-99% of cases)
Immunodeficiency	Very frequent (present in 80%-99% of cases)
Intellectual disability, mild	Very frequent (present in 80%-99% of cases)
Myopathy	Frequent (present in 30%-79% of cases)
Autosomal recessive inheritance	-
Broad nasal tip	-
Cardiomyopathy	-
Deeply set eye	-
Distal amyotrophy	-
Elevated hepatic transaminases	-
Elevated serum creatine phosphokinase	-
Hepatic fibrosis	-
Hepatomegaly	-
Hyperlipidemia	-
Malar flattening	-
Midface retrusion	-
Ventricular hypertrophy	-

Last updated: 9/1/2017

Cause Cause

Glycogen storage disease type 3 (GSDIII) is caused by changes (mutations) in the AGL gene. This gene provides instructions for making the glycogen debranching enzyme, which is involved in the breakdown of glycogen - an important source of stored energy in the body. Most mutations in the AGL gene lead to production of a non-working form of the glycogen debranching enzyme; these mutations are usually responsible for causing GSD types IIIa and IIIb. The mutations in the AGL gene that cause types IIIc and IIId presumably lead to the production of glycogen debranching enzyme with reduced function. All AGL mutations, however, lead to the increased buildup of abnormal, partially broken down glycogen within cells. This buildup damages tissues and organs in the body, thereby causing the signs and symptoms of GSDIII.^[3]

Last updated: 2/13/2012

Inheritance Inheritance

Glycogen storage disease type 3 (GSDIII) is inherited in an autosomal recessive manner. This means that mutations in both copies of the disease-causing gene (usually one inherited from each parent) are necessary to cause the condition. Individuals with one abnormal copy of the gene are referred to as carriers; carriers are unaffected and typically do not show any signs or symptoms of the condition. When two carriers for an autosomal recessive condition have children together, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of his/her parents, and a 25% chance to not be a carrier and not have the condition.

Last updated: 2/13/2012

Diagnosis Diagnosis

Glycogen storage disease type 3 (GSDIII) should be suspected when three main features are present: hepatomegaly (enlarged liver), ketotic hypoglycemia (low blood sugar accompanied by ketosis), and elevated serum concentration of transaminases (a type of enzyme) and CK. Debranching enzyme activity (which is deficient in individuals with the condition) can be measured in a liver biopsy, but this is now not typically necessary for diagnosis. Genetic testing of the AGL gene, the only gene known to be associated with GSDIII, confirms the diagnosis.^[2]

Last updated: 2/13/2012

Yes. GeneTests lists the names of laboratories that are performing genetic testing for GSDIII. To view the contact information for the clinical laboratories conducting testing, click here.

Please note: Most of the laboratories listed through GeneTests do not accept direct contact from patients and their families; therefore, if you are interested in learning more, you will need to work with a health care provider or a genetics professional.

Last updated: 2/13/2012

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment Treatment

There is not currently a cure for for glycogen storage disease type 3 (GSDIII). In some cases, diet therapy is helpful. Strict adherence to a dietary regimen may reduce liver size, prevent hypoglycemia (low blood sugar), help to reduce symptoms, and allow for growth and development.^[6] Management typically includes a high-protein diet with cornstarch supplementation to maintain a normal level of glucose in the blood. In infancy, feeding every three to four hours is typically recommended. Toward the end of the first year of life, cornstarch is usually tolerated and can be used to avoid hypoglycemia. A high-protein diet prevents breakdown of muscle protein in times of glucose need and preserves skeletal and cardiac muscles. Skeletal and cardiac myopathies may be improved with high-protein diet and avoiding excessive carbohydrate intake.^[2] Liver transplantation may be indicated for patients with hepatic cancers.^[6]

Individuals seeking personal treatment advice should speak with their health care provider.

Last updated: 2/13/2012

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.

Do you have updated information on this condition? Let us know.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Association for Glycogen Storage Disease
PO Box 896
Durant, IA 52747
Telephone: 1-563-514-4022
E-mail: info@agsdus.org
Website: http://www.agsdus.org
Association for Glycogen Storage Disease UK
Old Hambledon Racecourse
Sheardley Lane
Droxford, Southampton, SO32 3QY
United Kingdom
Telephone: 0300 123 2790 (Office hrs, Mon-Thurs) or 0300 123 2799 (Out of hours)
Website: http://www.agsd.org.uk/
Children Living with Inherited Metabolic Diseases (CLIMB)
Climb Building
176 Nantwich Road
Crewe CW2 6BG
United Kingdom
Toll-free: 0800 652 3181
Telephone: 0845 241 2173
E-mail: contact@climb.org.uk
Website: http://www.climb.org.uk
Children's Fund for Glycogen Storage Disease Research, Inc.
20 Sherwood Lane
Cheshire, CT 06410
Telephone: 203-272-7744
E-mail: info@curegsd.org
Website: http://www.cureGSD.org

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Glycogen storage disease type 3. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Glycogen storage disease type 3. Click on the link to view a sample search on this topic.

News & Events News & Events

News

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

I am the parent of a child with GSD type III. I would love to receive any information about the disease, treatments being done, research studies, etc. Thank you for your time. See answer
My son has been diagnosed with GSD type 3 based on liver biopsy. Is there another test to confirm this diagnosis? Are there any treatments available? See answer

Have a question? Contact a GARD Information Specialist.

References References

Glycogen storage disease type III. Genetics Home Reference. September 2010; http://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-iii. Accessed 3/1/2011.
Aditi Dagli, Christiaan P Sentner, David A Weinstein. Glycogen storage disease type III. GeneReviews. October 21, 2010; http://www.ncbi.nlm.nih.gov/books/NBK26372/. Accessed 3/2/2011.
Glycogen storage disease type III. Genetics Home Reference. September 2010; http://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-iii. Accessed 2/13/2012.
Roseline Froissart. Glycogen debranching enzyme deficiency. Orphanet. September 2009; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=366. Accessed 2/13/2012.
Forbes Disease. NORD. October 12, 2007; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/396/viewAbstract. Accessed 2/13/2012.
Wayne E Anderson. Glycogen Storage Disease, Type III: Treatment & Medication. eMedicine. January 13, 2010; http://emedicine.medscape.com/article/119597-treatment. Accessed 3/2/2011.