What are Glycogen Storage Diseases?

Inherited disorders

These are diseases that you get because of your genes or genetic make-up. You get your genes from your parents.

Metabolism

A huge number of chemical reactions take place in your body every day.

Most of these reactions are linked to using food to provide energy or to help your body grow and repair itself. If you have a disorder of metabolism (or metabolic disorder), there is a problem with one or more of those reactions.

Glucose

This is carbohydrate in one of its simplest forms. Blood glucose (sometimes called ‘blood sugar’) is one of the main energy sources for your body.

Hypoglycaemia

This means ‘low levels of glucose in the blood’. (This is different to ‘Hyperglycaemia’ which means ‘too much glucose in the blood’).
Hypo = Low
Hyper = High
Hypoglycaemia requires urgent attention.

Carbohydrate

One of the main nutrients that you get from food. Most of the carbohydrate in your diet comes from starchy foods such as bread, rice, pasta, noodles and potatoes. You can also get carbohydrates from sugary foods such as sweets, cakes, biscuits, jam, honey and syrup.

Glycogen

In simple terms, the body uses glycogen to store glucose that isn’t needed for immediate use. When blood glucose levels start to drop, glycogen can release glucose back into the blood.

If you have a liver GSD, there is an issue getting glucose from the glycogen stores.

As this is a term you may not be familiar with, take a look at the frequently asked questions on glycogen.

If you have a liver GSD, your glycogen metabolism doesn’t work properly. This needs careful lifelong management to avoid your blood glucose levels going too low and causing problems.

Beyond that, the management of GSD aims to support you to live a full and healthy life.

Common Symptoms

If you have a liver GSD, the aim of your management is to minimise symptoms and promote good health, growth and development. Symptoms can vary depending on which type of GSD you have (see below for more details).

Avoiding episodes of hypoglycaemia (sometimes referred to as a ‘hypo’) is a key priority. A ‘hypo’ occurs when blood glucose levels go too low.

Your Liver May Be Enlarged

Due to glycogen stores building up in your liver, it may become enlarged (the medical term is hepatomegaly).

From the outside, this can look like a large stomach which seems out of proportion with the rest of your body.

With good management, your liver will reduce in size over time.

Frequent eating

As your body cannot use its glycogen stores to keep blood glucose levels ‘topped up’, you need to eat frequently.

Young children, in particular, have high energy demands for their size. For example, with babies who have not yet been diagnosed, parents may comment on how regularly they cry for feeding.

Short Stature

To grow properly, children need energy.

In untreated individuals, there are problems with the body maintaining a steady energy supply. Unsurprisingly, this can interfere with growth and children with GSD may appear short for their age. However, with good management, growth will improve.

Different Types of Liver GSDs

The term Glycogen Storage Disease does not apply to just one condition. There are many different types. The main liver GSDs are outlined below.
Get more information on the type most relevant to you:

Type I or Von Gierke disease

In this type of Glycogen Storage Disease, your body cannot release glucose from the glycogen stores.

Ketotic types

Glycogen is a large branched structure which stores very high numbers of individual glucose units. When the body needs energy, the glycogen debranching enzyme ‘breaks off’ a branch from the large glycogen structure.

In type III, the glycogen debranching enzyme does not work as well as it should. This can result in you having low levels of glucose.

Deficient enzyme: Amylo-1,6-glucosidase This enzyme is sometimes referred to as the glycogen debranching enzyme.

GSD III is split into two main types. Both GSD type IIIa and IIIb affect the liver but GSD IIIa also affects the muscles.

Muscle weakness

If you have GSD type IIIa, your body cannot use your muscle’s glycogen stores. This can lead to muscle weakness - you may tire more easily than others. You may also have leg pain.

When you exercise, you may need extra resting time and extra snacks. Your Specialist Dietitian will advise on this.

Heart

The heart is arguably the most important muscle in the body. If you have GSD type IIIa, the heart can become enlarged. This is referred to as cardiomyopathy. Management of this condition aims to reduce any complications. Regular heart scans are used to monitor the heart.

The breakdown of glycogen is done in several stages. One of the stages involves the production of glucose-1-phosphate (G1P) which is then turned into glucose and used for energy.

If you have GSD type VI, the enzyme needed to produce G1P is not working as well as it should be. This can lead to you having low levels of G1P and therefore low blood levels of glucose.

Deficient enzyme: Liver glycogen phosphorylase

In most cases of GSD type VI, the enzyme works more slowly than normal, but it still works. Therefore, you will still make glucose but in lower quantities than other people.

Type VI is often viewed as a milder form of GSD. If you have this type, it is still very important that you attend all your clinic appointments and follow the advice given to you by your Specialist Metabolic Team.

Type IX is similar to type VI, as you can still make glucose, but in a lower quantity. Therefore, types VI and IX can produce very similar symptoms.

One of the stages in the breakdown of glycogen involves the production of glucose-1-phosphate (G1P), which can be turned into glucose.

In type IX, the enzyme required to produce G1P can work but it doesn’t get ‘switched on’. There are low levels of G1P and therefore low blood levels of glucose.

Deficient enzyme: Phosphorylase Kinase

Type IX can be very variable in terms of severity. Some individuals are prone to regular ‘hypos’. Others, without treatment, show poor growth and an enlarged liver but don’t tend to get ‘hypos’.

It is often viewed as a milder form of GSD. It is still very important that you attend your medical appointments and follow the advice given to you by your Specialist Metabolic Team.

GSD type 0, in some ways, is very different to the other glycogen storage diseases. With the other liver GSDs, there is an inability to release glucose from the glycogen stores. In type 0 you are unable to build up your glycogen stores in the first place.

Deficient enzyme: Glycogen synthase

Type 0 leads to fluctuating glucose levels when it is not properly managed:

Glucose will build to high levels after a meal because your body cannot store it as glycogen. High levels of glucose are not typically seen in the other liver GSDs.
Once this glucose is used up, you will develop hypoglycaemia or low levels of glucose in the blood.

Practical implications for ketotic types

Alternative energy sources

When your glucose levels are low, your body needs to produce energy in other ways. One way to do this involves your body using its fat stores to produce ketones. Your body can also start to use protein to produce energy.

What are ketones

They are an alternative source of energy. In healthy individuals, ketone levels are typically very low.

Ketones are produced from your body’s fat stores. The brain needs a lot of energy to work properly but it cannot use fat to produce energy – it prefers glucose. However, your brain can get energy from ketones.

If you have a liver GSD, turning fat into ketones helps your brain, and other muscles, get energy when glucose levels are low.

Although ketones can be a very useful source of energy, it is important that your levels are controlled.

Management

Good dietary management aims to reduce the risk of your blood glucose levels going too low. This means that your body will not need to make ketones or break down your muscles to produce energy.

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