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Genetic and Rare Diseases Information Center (GARD)

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Glycogen storage disease type 3


Other Names for this Disease
  • Amylo-1,6-glucosidase deficiency
  • Cori disease
  • Forbes disease
  • Glycogen debrancher deficiency
  • Limit dextrinosis
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Overview



What is glycogen storage disease type 3?

What are the signs and symptoms of glycogen storage disease type 3?

What causes glycogen storage disease type 3?

How is glycogen storage disease type 3 inherited?

Is genetic testing available for glycogen storage disease type 3?

How is glycogen storage disease type 3 diagnosed?

How might glycogen storage disease type 3 be treated?


What is glycogen storage disease type 3?

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

What are the signs and symptoms of glycogen storage disease type 3?

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

What causes glycogen storage disease type 3?

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

How is glycogen storage disease type 3 inherited?

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

Is genetic testing available for glycogen storage disease type 3?

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

How is glycogen storage disease type 3 diagnosed?

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

How might glycogen storage disease type 3 be treated?

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

References
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. Forbes Disease. NORD. October 12, 2007; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/396/viewAbstract. Accessed 2/13/2012.
  6. 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.