Genetic testing for GSD1 (Glycogen storage disease type I) – Von Gierke disease

Glycogen storage disorder type I (also known as GDS1 and Von Gierke disease) is a hereditary disorder that disrupts the ability to break down and use glycogen, a stored form of glucose.


Glycogen storage disorders

Glycogen is a glucose polymer, which means it comprises many units of chemically attached glucose. Glycogen is a storage form with great importance to the body’s short- and medium-term energy storage.

When the glucose storage in the blood runs out after eating, our body begins breaking down glycogen in the liver to supply glucose to the organs. Glycogen buildup and breakdown mechanisms contain several enzymes, deficiencies in these enzymes lead to glycogen storage disorders. These diseases differ in symptoms and effected organs, depending on the deficient enzyme.


The genetic basis of GSD1

Von Gierke disease is caused by a deficiency in the glucose-6-phosphatase enzyme. Phosphate group removal signals the cells to release glucose. Deficiency in this enzyme leads to excess amounts of glucose in the cells.

Glucose cannot leave the cell and reach other organs. Since glycogen synthesis occurs mostly in the liver, the liver cannot provide glucose from these storages to the blood stream and other organs.

The most common type of GSD is 1a. In this disease, the deficient enzyme is 6-phosphate hydrolase. Other types (such as 1b, 1c, or 1d) are linked to deficiencies in other enzymes in the process of glucose metabolism.

This disease has an autosomal recessive inheritance pattern. This means that the risk for two carrier parents for having a child with this disease is 25%. Two mutated copies of the gene are required to develop the disorder. GSD1 is considered a rare disease, its prevalence is estimated is 1 in 100,000 people.

The mutated gene is located on chromosome 11. There are several common mutations that may cause this disease, which vary according to ethnic descent. For example, the mutation R83C is prevalent in people of Ashkenazi Jewish descent.


Signs and symptoms

People with GSD1 suffer from an enlarged liver caused by the accumulation of glycogen in the cells. In addition, they often suffer from hypoglycemia – dangerously low blood sugar, and from lactic acidosis. These are caused by a glucose deficiency in the cells, especially after extended time between meals.

Patients suffer from growth delay, short stature, kidney defects, and metabolic changes. In adulthood, they are at an increased risk for hepatic adenoma (liver tumors), a condition that requires follow-up for a rapid treatment of complications.



Treatment of Von Gierke disease includes refraining from long times of fasting that lead to cellular hunger due to the lack of glucose. To avoid this condition, patients require frequent meals and overnight tube feeding that contains starch (the equivalent of glycogen in plants). A continuous delivery of glucose can prevent the body’s dependency on the dysfunctional glycogen stores.


Diagnosis and genetic testing

In cases of a risk for GSD1, genetic testing can help detect common gene mutations. Full gene sequencing can be performed due to the presence of unknown mutations.

Since not all gene mutations are known, and the clinical meaning of these mutations is not always fully understood, liver biopsies are recommended in cases of a risk for GSD1 without a known mutation.

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