Hers disease – genetic testing for glycogen storage disease type VI

Hers disease, also known as glycogen storage disease type VI, is disease caused by a gene mutation that impairs glycogen storage metabolism. This disease is named after Henri-Géry Hers, one of the researchers that interpreted lysosomal storage diseases.

Glycogen is a molecule built of glucose base-units, that helps keep a stable level of glucose in our bloodstream between mealtimes. It is a polysaccharide found mainly in the muscles and liver but also in other tissues, such as in the kidneys.

Glycogen is formed when glucose levels in the cells are sufficient and the need to store excess glucose arises. Certain Enzymes bind glucose molecules to create glycogen which is a ready source that can be broken down to its base-units at need.

All this is true in healthy people, but in people with glycogen storage diseases, there is a deficiency in an enzyme that takes part in glycogen breakdown or buildup. In these cases, molecules cannot be broken down and instead are accumulated unproportionally. 


What are the symptoms?

The main symptom of Hers disease is hepatomegaly (an enlarged liver). In addition, people with GSD type VI suffer from growth delay, and hyperlipidemia with mild hypoglycemia and hyperketosis. Glucagon administration showed minor effect in these patients.

It is important to note that in most cases, symptoms tend to improve with age and many adults with this disease show no symptoms at all when they reach adulthood. This is a rare disease, but it may have a higher prevalence. Since clinical manifestation is so mild, the disease may be underdiagnosed.


Which genes are involved?

The disease is caused by a mutation in the gene PYGL, located on chromosome 14. This gene is coded to an enzyme that takes part in glycogen breakdown only in the liver, so unlike other glycogen storage disorders, symptoms of this disease do not include muscle impairments.

The relevant enzyme is called liver glycogen phosphorylase. As of today, seventeen gene mutations that can cause Hers disease have been identified.


Diagnosis and genetic testing

Hers disease diagnosis is based on symptoms such as hepatomegaly or growth delay. Genetic testing of the PYGL gene can be used to confirm this diagnosis. When genetic testing results are unclear or cannot be confirmed, a liver biopsy is performed.

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