Glycogen storage disease type 6

Title

Other Names:

GSD6; Glycogen storage disease 6; Hers disease; GSD6; Glycogen storage disease 6; Hers disease; Phosphorylase deficiency glycogen-storage disease of liver See More

Categories:

Congenital and Genetic Diseases; Digestive Diseases; Metabolic disorders

Summary Summary

Glycogen storage disease type 6 (GSD6) is a genetic disease in which the liver cannot process sugar properly.^[1] The liver is responsible for breaking down a substance called glycogen. Glycogen is the stored form of sugar that is made by breaking down carbohydrates.^[2] When the liver cannot break down glycogen properly it causes a buildup that is damaging to the body. Symptoms of the disease usually begin in infancy or childhood and include low blood sugar (hypoglycemia), an enlarged liver (hepatomegaly), and an increase in the amount of lactic acid in the blood (lactic acidosis). These symptoms are especially likely to occur when an individual does not eat for a long time. Symptoms tend to improve as people with this disease get older. The disease is especially common in the Mennonite population.^[1]

GSD6 is caused by mutations (changes) in the PYGL gene. The disease is inherited in an autosomal recessive manner.^[1] The diagnosis is made based on genetic testing of the PYGL gene. A liver biopsy that tests the function of liver glycogen phosphorylase may be necessary if the results of the genetic testing are inconclusive. Treatment may include eating frequent meals that are high in carbohydrates.^[2]

Last updated: 10/12/2017

Symptoms Symptoms

Symptoms of GSD6 usually begin in infancy or childhood and may include an enlarged liver (hepatomegaly). Other symptoms of the disease include low blood sugar (hypoglycemia) or an increase in the amount of lactic acid in the blood (lactic acidosis). Hypoglycemia can also cause symptoms such as faintness, weakness, hunger, and nervousness.^[2] The symptoms of the disease are especially likely to occur when an individual does not eat for a long time.^[1] In some cases, children with glycogen storage disease type 6 have slow growth (growth retardation) or muscle weakness (hypotonia).^[2]

People with GSD6 may be at an increased risk to have liver cancer or an enlarged heart (cardiomyopathy).^[3]^[4] Many of the symptoms of GSD6 tend to improve as the child gets older. Adults with the disease frequently do not have hepatomegaly, and they are not expected to be shorter than other individuals.^[2]

Last updated: 10/12/2017

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)
Hypoglycemia	Very frequent (present in 80%-99% of cases)
Autosomal recessive inheritance	-
Hepatomegaly	-
Hyperlipidemia	-
Increased hepatic glycogen content	-
Postnatal growth retardation	-

Last updated: 10/1/2017

Cause Cause

GSD6 is caused by changes or mutations in the PYGL gene. This gene is responsible for telling the body how to make an enzyme called liver glycogen phosphorylase. This enzyme is partly responsible for breaking down glycogen. Glycogen is a form of energy that comes from carbohydrates and is stored in the liver. When the body needs more energy, glycogen in the liver is broken down by glycogen phosphorylase.^[1]

When there are mutations in the PYGL gene, there is not enough functioning glycogen phosphorylase to break down glycogen. Therefore, glycogen starts to build up in the liver cells, which causes hepatomegaly. This also means that the body does not get enough energy, which causes symptoms such as hypoglycemia and lactic acidosis.^[1]

Last updated: 10/12/2017

Inheritance Inheritance

GSD6 is inherited in an autosomal recessive manner.^[1] This means that both copies of the PYGL gene must be changed in order to have symptoms of the disease. We inherit one copy of each gene from our mother and the other from our father.

People with a mutation in only one copy of the PYGL gene are known as carriers. Most carriers do not have any symptoms of the disease. When two carriers of glycogen storage disease type 6 have children together, for each child there is a:

25% chance that the child will have glycogen storage disease type 6
50% chance that the child will be a carrier of glycogen storage disease type 6 like the parents
25% chance that the child will have two working copies of PYGL, so the child will not have glycogen storage disease type 6 and will not be a carrier.

Last updated: 10/12/2017

Diagnosis Diagnosis

GSD6 is diagnosed when a healthcare provider observes signs and symptoms of the disease such as an enlarged liver and hypoglycemia.^[5] The diagnosis is made based on genetic testing of the PYGL gene. A liver biopsy that tests the function of liver glycogen phosphorylase may be necessary if the results of the genetic testing are not clear.^[4]

Last updated: 10/12/2017

Treatment Treatment

The primary treatment for GSD6 is to avoid prolonged periods of time without eating. Because glycogen is only broken down when stored energy is needed, eating frequent meals can avoid the need to break down glycogen. Levels of blood glucose should be monitored to make sure that the diet is working properly.^[2]^[4] This will minimize the symptoms of the disease. In some cases, no other treatment is necessary. Uncooked cornstarch may be helpful for some people with GSD6. Uncooked cornstarch is a complex carbohydrate that is difficult for the body to digest; therefore it maintains normal blood sugar levels for a longer period of time than most carbohydrates in food.^[2]^[3]^[4]^[6] For children who have muscle weakness, a high-protein diet may also be recommended.^[3]^[5]

Last updated: 10/12/2017

Prognosis Prognosis

The signs and symptoms of GSD6 tend to improve with age. In general, it is thought that the body can adapt to low blood sugar levels and produce energy through alternate methods.^[2] Therefore, the long-term outlook for people affected by the disease is often good. However, if the symptoms of the disease are not well controlled with diet, additional symptoms such as delayed puberty and osteoporosis may develop.^[4]

Adults are typically of a normal height and do not have muscle weakness. Liver problems associated with the disease tend to resolve as people get older, and the need for treatment for liver problems is rare in adulthood.^[5]

Last updated: 10/12/2017

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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

Social Networking Websites

Canadian Association for Glycogen Storage Disease
P.O Box 56009
Vancouver
British Columbia
V5L5E2 Canada
Website: https://www.facebook.com/canadianagsd/

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Living With Living With

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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

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 6. Click on the link to view a sample search on this topic.

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When a person has an autosomal recessive condition like glycogen storage disease type VI, what is the likelihood that their child will have the disorder? See answer

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References References

Glycogen storage disease type VI. Genetics Home Reference. September 2010; http://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-vi.
Hers Disease. National Organization for Rare Disorders. 2007; https://rarediseases.org/rare-diseases/hers-disease/.
Roscher A, Patel J, Hewson S, Nagy L, Feigenbaum A, Kronick J, Raiman J, Schulze A, Siriwardena K, and Mercimek-Mahmutoglu S. The natural history of glycogen storage diseases type VI and IX: Long-term outcome from the largest metabolic center in Canada. Molecular Genetics and Metabolism. November 2014; 113(3):171-176. https://www.ncbi.nlm.nih.gov/pubmed/25266922.
Dagli AI and Weinstein DA. Glycogen Storage Disease Type VI. GeneReviews. May 17, 2011; https://www.ncbi.nlm.nih.gov/books/NBK5941/.
Anderson WE. Type VI Glycogen Storage Disease. Medscape Reference. December 5, 2014; http://emedicine.medscape.com/article/119873-overview.
Type VI Glycogen Storage Disease. Association for Glycogen Storage Disease. http://www.agsdus.org/type-vi.php. Accessed 10/4/2017.