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Disease Profile

Glycogen storage disease type 3

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

US Estimated

Europe Estimated

Age of onset

Infancy

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ICD-10

E74.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Forbes disease; Cori disease; Limit dextrinosis;

Categories

Congenital and Genetic Diseases; Digestive Diseases; Heart Diseases;

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 highprotein 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]

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]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Full cheeks
Apple cheeks
Big cheeks
Increased size of cheeks
Large cheeks

[ more ]

 0000293
Hypertriglyceridemia
Increased plasma triglycerides
Increased serum triglycerides
Increased triglycerides

[ more ]

 0002155
Hypoglycemia
Low blood sugar
0001943
Immunodeficiency
Decreased immune function
0002721
Intellectual disability, mild
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation

[ more ]

 0001256
Short stature
Decreased body height
Small stature

[ more ]

 0004322
30%-79% of people have these symptoms
Myopathy
Muscle tissue disease
0003198
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Broad nasal tip
Broad tip of nose
Broad, upturned nose
Increased breadth of nasal tip
Increased breadth of tip of nose
Increased width of nasal tip
Increased width of tip of nose
Nasal tip, broad
Nasal tip, wide
Wide tip of nose

[ more ]

 0000455
Cardiomyopathy
Disease of the heart muscle
0001638
Deeply set eye
Deep set eye
Deep-set eyes
Sunken eye

[ more ]

 0000490
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

 0005280
Distal amyotrophy
Distal muscle wasting
0003693
Elevated hepatic transaminase
High liver enzymes
0002910
Elevated serum creatine kinase
Elevated blood creatine phosphokinase
Elevated circulating creatine phosphokinase
Elevated creatine kinase
Elevated serum CPK
Elevated serum creatine phosphokinase
High serum creatine kinase
Increased CPK
Increased creatine kinase
Increased creatine phosphokinase
Increased serum CK
Increased serum creatine kinase
Increased serum creatine phosphokinase

[ more ]

 0003236
Hepatic fibrosis
0001395
Hepatomegaly
Enlarged liver
0002240
Hyperlipidemia
Elevated lipids in blood
0003077
Malar flattening
Zygomatic flattening
0000272
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface

[ more ]

 0011800
Muscle weakness
Muscular weakness
0001324
Thin upper lip vermilion
Thin upper lip
0000219
Thin vermilion border
Decreased volume of lip
Thin lips

[ more ]

 0000233
Ventricular hypertrophy
0001714
Do you have updated information on this disease? We want to hear from you.

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]

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]

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

    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 highprotein 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.

    Management Guidelines

    • 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.

      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

        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

          • 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.
          • 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.

            References

            1. Glycogen storage disease type III. Genetics Home Reference. September 2010; https://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; https://www.ncbi.nlm.nih.gov/books/NBK26372/. Accessed 3/2/2011.
            3. Glycogen storage disease type III. Genetics Home Reference. September 2010; https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-iii. Accessed 2/13/2012.
            4. Roseline Froissart. Glycogen debranching enzyme deficiency. Orphanet. September 2009; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=366. Accessed 2/13/2012.
            5. Forbes Disease. NORD. October 12, 2007; https://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; https://emedicine.medscape.com/article/119597-treatment. Accessed 3/2/2011.

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