Andersen disease – genetic testing for glycogen storage disease type IV

Andersen disease, also known as glycogen storage disease type IV (also GSD type IV), is a hereditary disorder that belongs to a group of disorders caused by a deficiency in the body’s glycogen stores.



In GSD type IV, the mutated gene is linked to building glycogen structures in the cells. Glycogen is not a simple chain of glucose groups but is structured in a branched chain. This structure is important to glycogen’s function as a form of energy storage, with maximum utilization of the cells’ storage capacity.

Glycogen branching enzyme is a special enzyme responsible for creating branching points in glycogen. Mutations in the gene coded to this enzyme cause the disease to develop. The glycogen created in this case is dysfunctional.

This disease has an autosomal recessive inheritance pattern. This means that for a child to develop the disease, they must inherit two mutated gene copies – one from each parent. In average, only one in four children of two mutated gene carriers will develop the disease. The mutated gene is located on chromosome 3 (3q14). Many different gene mutations are associated with this disorder.


Glycogen storage diseases

Glycogen is a form of storage in the body. It is made up of many molecules of glucose – the main type of sugar used by our body. When excess glucose exists in the bloodstream, the liver gathers this excess glucose and creates glycogen chains in the cells.

When the need for accessible energy arises (such as at night, long after dinner), the liver breaks down glycogen into its base-units (glucose) and releases them into the bloodstream where they can reach the cells.

Glycogen storage diseases (also known as GSD) are a group of diseases caused by a defect in glycogen function. There are several kinds of GSDs, one of them being Andersen’s disease.


Signs and symptoms

Disease severity depends, among other factors, on the mutated protein’s expression. When there is no protein expression, symptoms will be more severe. In cases of a relative lack of protein, the disease can be milder and appear only later in life.

Severe presentation at a young age can include severe heart defects and leads to death during the first months of life. Typical symptoms include an enlarged liver and spleen, and failure to thrive. Later stages of the disease include hypoglycemia (decreased levels of glucose in the bloodstream) that can be life threatening.

The disease progresses to liver cirrhosis, esophageal varices, and liver failure. Less common types of this disease are less severe and develop later in life.

This disease is typically divided into several variants: Congenital, Childhood-onset, and Adult-onset.



Diagnosis of Andersen disease is based on testing enzyme levels in skin or muscle biopsies. More modern diagnosis is based on detecting mutation in the gene GBE.

This disease can be diagnosed during routine prenatal testing when parents are known to be carriers. Screening methods can include amniocentesis or chorionic villus sampling



There is currently no treatment for Andersen’s disease. The deficient enzyme cannot be replaced, nor is there effective gene therapy. Several attempts were made to treat the disease via liver transplants, with relative success. 

Cells in the transplanted organ contain the donor’s genetic material, therefore the relevant enzyme is not deficient, and the liver can break down glycogen normally. However, it should be noted that the deficient enzyme can be found in other body cells (such as in the muscles and heart), and that a liver transplant is a complicated procedure that carries a risk for complications and requires medication that carries significant side effects.

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