Genetic tests for GSD – Glycogen storage disease

Glycogen is a complex molecule that serves as a source of glucose in our body. Our cells need glucose to produce energy. Since cell life functions cannot be performed without accessible energy, the cells cannot function normally without glucose. Though fatty acids and proteins can fill energy needs, the most important substance in the short term is glucose.

After meals, glucose levels in the blood rise and there is plenty of glucose to be distributed to body tissues. Between meals, during sleep or when fasting, there is no available glucose supply from our digestive system. Glycogen – a branched polymer of glucose – is broken down to overcome such situations. Glycogen s composed of a large, branched chain of glucose units.

In cases of excess glucose in the blood, the body stores the glycogen, mainly in the liver. When the body needs glucose, glycogen is broken down to its basic units and released from the liver into the blood stream. Glycogen synthesis also occurs in the muscles and heart, though foe their own use and not for the use of other body tissues. 

Glycogen storage diseases

Glycogen storage disease is a group of inherited diseases in which an enzyme defect in the glycogen use process leads to a metabolic disorder in the body. This damage can occur in all organs that produce glycogen, or only in certain organs.

There are at least seven types of GSD, some even classify up to twelve diseases with different sub-types. Some of these diseases have names (von Gierke’s disease, McArdle’s disease, Cori disease), but the diseases are commonly known today by numbered types – type 1 glycogen storage disease, type 2. Etc.


GSD classifications

Glycogen storage disorder is classified according to the affected tissue. Since glycogen is especially common in liver and muscle cells, these are the main tissues affected. The heart Is another organ targeted by these diseases. GSD types 1 and 6 mainly cause damage to the liver. GSD type 2 (Pompe’s disease) mainly affects the heart, and types 3, 5 and 7 mainly affect the muscles.


What are the main glycogen storage diseases?

Von Gierke’s disease – Type I – the most common type of GSD. In this type, the liver’s ability to release glucose is damaged, which causes glycogen to accumulate in the cells.

Pompe’s disease – type II – mainly affects the hearts muscles. People with Pompe’s disease have an enlarged heart and heart failure. Enzyme replacement therapy is available for this condition.

Cori’s disease – Type III – this disease damages the enzyme that helps break down glycogen branches (this enzyme is known as debranching enzyme). Affects the muscle tissues.

Andersen disease – Type IV – damages the enzyme that creates glycogen branching.

McArdle’s disease – Type V – this disease damages the enzyme that releases glucose from glycogen in the muscles. Leads to muscle tissue damage and kidney failure.

Her’s disease – Type VI – damages the enzyme that releases glucose from glycogen in the liver. Leads to an enlarged liver and low blood sugar.

Tarui’s disease – Type VII – this disease harms the enzyme in charge of glycogen usage (glycolysis). This causes glycogen to accumulate in the cells, glucose cannot be broken down and used. This disease causes damage to the muscles which leads to exertional fatigue. 


Genetic causes of GSD

Glycogen storage disease has an autosomal recessive inheritance. This means that two copies of the defected gene are needed to develop the condition. A child can be born with GSD only if both parents are carriers. Genetic testing for this disease can be performed before marriage or pregnancy.

The most common form of GSD is von Gierke’s disease (GSD type I). These are usually rare hereditary diseases.

Certain types of GSD are more prevalent in certain populations. Types I and VII are more prevalent in people of Ashkenazi Jewish descent and type III is prevalent among people of North-African Jewish descent.

In most cases, these populations have a specific gene mutation known as a founder mutation. This mutation is usually a result of a mutation that appears in small population groups where inbreeding has caused its higher prevalence.


GSD symptoms vary according to the affected enzymes and tissues. When the main affected area is the liver, the disease causes an enlarged liver (due to glycogen accumulation) and hypoglycemia (low levels of glucose in the blood).

When the main area damaged are the muscles, the result is exertional fatigue due to a lack of energy that is available to the muscles.

Pompe’s disease (type II) can lead to heart failure and an abnormally large heart.

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