Rare Hematology News

Disease Profile

Glycogen storage disease type 6

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.


US Estimated

Europe Estimated

Age of onset






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


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.


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.


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


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.


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.


Not applicable


Other names (AKA)

GSD6; Glycogen storage disease 6; Hers disease;


Congenital and Genetic Diseases; Digestive Diseases; Metabolic disorders


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]


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]

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:
80%-99% of people have these symptoms
Enlarged liver
Increased hepatic glycogen content
30%-79% of people have these symptoms
Delayed puberty
Delayed pubertal development
Delayed pubertal growth
Pubertal delay

[ more ]

Elevated hepatic transaminase
High liver enzymes
Failure to thrive
Faltering weight
Weight faltering

[ more ]

Low blood sugar
High levels of ketone bodies
5%-29% of people have these symptoms
Abdominal distention
Abdominal bloating
Abdominal swelling
Belly bloating

[ more ]

Exercise-induced muscle cramps
Exercise-induced muscle cramping
Muscle cramps following exercise
Muscle cramps on exercise
Muscle cramps on exertion
Muscle cramps with exertion

[ more ]

Hepatic fibrosis
Elevated lipids in blood
Intermittent lactic acidemia
Motor delay
Muscular hypotonia
Low or weak muscle tone
Portal fibrosis
Postexertional malaise
Short stature
Decreased body height
Small stature

[ more ]

Sleep disturbance
Difficulty sleeping
Trouble sleeping

[ more ]

1%-4% of people have these symptoms
Abnormality of the kidney
Abnormal kidney
Scar tissue replaces healthy tissue in the liver
Hepatocellular carcinoma
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
Postprandial hyperlactemia
High urine protein levels
Protein in urine

[ more ]

Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
Failure to thrive in infancy
Faltering weight in infancy
Weight faltering in infancy

[ more ]

Elevated serum cholesterol
Elevated total cholesterol
Increased total cholesterol

[ more ]

Increased plasma triglycerides
Increased serum triglycerides
Increased triglycerides

[ more ]

Postnatal growth retardation
Growth delay as children


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]


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]


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 highprotein diet may also be recommended.[3][5]


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

    Social Networking Websites

      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.


          1. Glycogen storage disease type VI. Genetics Home Reference. September 2010; https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-vi.
          2. Hers Disease. National Organization for Rare Disorders. 2007; https://rarediseases.org/rare-diseases/hers-disease/.
          3. 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.
          4. Dagli AI and Weinstein DA. Glycogen Storage Disease Type VI. GeneReviews. May 17, 2011; https://www.ncbi.nlm.nih.gov/books/NBK5941/.
          5. Anderson WE. Type VI Glycogen Storage Disease. Medscape Reference. December 5, 2014; https://emedicine.medscape.com/article/119873-overview.
          6. Type VI Glycogen Storage Disease. Association for Glycogen Storage Disease. https://www.agsdus.org/type-vi.php. Accessed 10/4/2017.

          Rare Hematology News