Glycogen Storage Disease Type III

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Glycogen Storage Disease Type III is caused by a problem in the AGL gene. The AGL gene provides instructions for making something called the glycogen debranching enzyme. The glycogen debranching enzyme breaks down glycogen. Glycogen is a major source of stored energy in your body and is what your body partly uses for fuel.

Problems in the AGL gene lead to a storage of abnormal and partially broken-down glycogen molecules within cells. A build up of abnormal glycogen can damage organs and tissues throughout the body, particularly affecting the liver and muscles. This then leads to the signs and symptoms of GS3.

There are 4 types of GSD3; GSD3A, GSD3B, GSD3C, GSD3D. The types are distinguished by their signs and symptoms. Typically, GSD3A and GSD3C affect the liver and muscles and GSD3B and CSD3D affect only the liver. It is often very difficult to distinguish between the types of GSD3, however GSD3A and GSD3B are the most common forms of the condition.

GSD3 affects 1 in 100, 000 people. It is often seen more frequently in people of North African Jewish ancestry, affecting 1 in 5,500 people. GSD3A is the most common form and is thought to affect 85% of all diagnosed cases. It is believed there are 150 people in the UK living with GSD3.

GSD3 typically begins in infancy and progresses throughout childhood.

Symptoms include;

• Low blood sugar levels
• Excess amounts of fats in the blood
• Elevated blood levels of liver enzymes.
• Enlarged liver (this usually returns to normal during adolescence, however some patients can develop chronic liver disease and liver failure later in life).
• Slow growth and short stature.
• Noncancerous tumours typically found in the liver.
• Muscle weakness – which can affect the heart and muscles used for movement.
• Poor muscle tone.

In infancy GSD3 can be fatal due to seizures called by low blood sugar. It is recommended that a high-protein diet and frequent feeds (every 3-4 hours) are maintained. Following diagnosis, you will be referred to a metabolic specialist and dietician, specialists will provide you with a special dietary plan which is important to follow. The exact lifespan of patients with GSD3 is unknown, however many patients live well into adulthood.

Children are usually diagnosed because they have a noticeable swollen abdomen due to an enlarged liver. Patients are also diagnosed via blood tests; testing for low blood sugar and a high level of fats. Health professionals will usually review a patient’s history, test results and symptoms before making a diagnosis.

If you suspect you have GSD3, we recommend you speak to your doctor in the first instance. GSD3 is difficult to diagnosis and will require further genetic testing.

Patients with GSD3 will be referred to specialist dietician who will provide a specialist diet. Infants and children are usually treated via a high-protein diet administered every 3-4 hours. In some cases, cornstarch (like glycogen) may be introduced in the first year and the dose/frequency will be determined by the specialist dietician via a process called titration. It is essential for patients with GSD3 to maintain their specialised diet to prevent becoming unwell. It is important that patients do not change their diet without consulting a specialist dietician first.

Patients living with GSD3 may suffer from an enlarged and damaged liver, therefore in these instances a liver transplant will be considered.

The BIMDG provide standard and emergency guidelines for patients with GSD3 and these can be found here; http://www.bimdg.org.uk/guidelines/guidelines-start.asp. These guidelines should be shared with your General Practitioner and emergency care staff in A&E. Symptoms of GSD3 will often escalate in the event of illness (such as the common cold) or refusal to feed.

At present there is no clinical trial relating to the treatment of GSD3 taking place.

Patients with GSD3 should be monitored annually by liver ultrasounds and frequent blood tests. If you or someone you know has been affected by GSD 3 you may want to consider genetic counselling, you will need to speak to your GP or metabolic specialist for a referral to a genetic counsellor. If you would like more information about genetic counselling, a toolkit can be found on the Metabolic Support UK website.

GSD 3 has autosomal recessive inheritance pattern. Humans have chromosomes made up of DNA. Genes are pieces of DNA that carry the genetic information. Each chromosome may have several thousand genes. We inherit chromosomes from the egg of the mother and sperm of the father. The genes on those chromosomes carry the instructions that determine a person’s characteristics, which are a combination of the parents.  

The pattern of inheritance of GSD 3 is autosomal recessive. This means that carriers of the condition do not have the disorder because the other gene of this pair is working normally. Parents of children with glycogen storage disease type XI are carriers.   

When both parents are carriers, the risk to the baby in each pregnancy is  

• 25% chance (1 in 4) of developing the condition  
•  50% chance (1 in 2) for the baby to be a carrier of the condition  
•  25% chance (1 in 4) for the baby to have two working genes and neither have the condition nor be a carrier  

Genetic counselling can be requested to get a full explanation.  

It is recommended that individuals from more frequently populations, such as the North African Jewish Community get tested.

For more information, please visit Association for Glycogen Storage Disease UK.

References are available on request. Please contact Helen Morris by phoning 0845 241 2173 or emailing helen@metabolicsupportuk.org [Resource Library No: AAP002].