Glycogen storage disease type 6

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.

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.

GSD6 is diagnosed when a healthcare provider observes signs and symptoms of the disease such as an enlarged liver and hypoglycemia. 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.

GSD6 is inherited in an autosomal recessive manner. 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.

The chance that a child of an individual who has glycogen storage disease type 6 will also have this condition depends on whether the unaffected parent is a carrier of this disease.

• If the unaffected parent is not a carrier, each child will not be affected but will be a carrier for this condition.
• If the unaffected parent is a carrier, each child has a 50% chance of being affected by the condition and a 50% chance of being an unaffected carrier.

Genetic testing may help to determine if the unaffected parent is a carrier, and speaking with a genetics professional may help a couple to better understand the chance of future offspring inheriting this condition.

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. 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.

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.

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. 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. For children who have muscle weakness, a high-protein diet may also be recommended.