Glycogen Storage Disease Type I (GSD-I) | Von Gierke Disease

Glycogen storage disease type I (GSD-I) is an autosomal recessive disease in which the liver can’t metabolize stored glycogen into glucose. GSDI occurs in 1 per 100,000 people.

In healthy people, the liver metabolizes glycogen into glucose to supply energy and maintain blood glucose at a healthy level. There are two subtypes of GSD-I, according to the type of the mutated gene. GSDIa is due to the mutation of the G6PC gene, while GSDIb is due to the mutated SLC37A4 gene. Mutation in one of two genes (G6PC or SLC37A4) causes a deficiency of enzymes, such as glucose 6 -phosphatase (G6Pase), which leads to glycogen accumulation in the liver and low blood glucose levels. Also, the deficiency of this enzyme causes the accumulation of other metabolites, such as uric acid, lactic acid, and lipids in our body. This accumulation leads to enlargement of the liver and kidneys.

The main symptom is hypoglycemia, which presents with tremors, seizures, growth retardation, and weak muscles. The elevated lipids lead to a yellow nodule in the skin near the joint (xanthomas). Accumulation of other metabolites leads to osteoporosis and gout. Also, the patient may have a bleeding tendency and liver adenomas.

Your child’s doctor can diagnose GSDI by laboratory investigations that show either your child has hypoglycemia and high levels of metabolites or not. If your child’s doctor suspected this disease, he would ask you to do a molecular genetic test for your child to confirm the diagnosis. Your child’s doctor may need a liver biopsy to detect specific enzyme deficiencies.

Your child’s doctor will order you to feed him some types of food like cornstarch to increase blood glucose and prevent hypoglycemia. Also, he will use drugs to decrease the uric acid level. Your child may need surgery to remove liver adenomas.

Now, let’s see this disease in more detail. We will discuss the following:

  • What causes this disease, and who is at risk of having it?
  • What are its symptoms, signs, and complication?
  • How will the doctor diagnose if I have this disease and confirm this diagnosis?
  • How can my doctor treat me? And what are the treatment options that I have?
  • What is the prognosis of GSDI?

Causes of Glycogen storage disease type I

Mutation in one of two genes (G6PC or SLC37A4) is the direct cause of GSDI. These genes share in the glycogen metabolism. Mutated G6PC gene leads to a glucose-6-phosphatase enzyme (G6Pase) deficiency, which hydrolyzes glucose- 6- phosphate to produce free phosphate and glucose. This mutation represents 80% of GSDI cases. Mutations in the SLC37A4 gene lead to a lack of the glucose-6-phosphatase translocase enzyme that acts as a transporter to the products and free glucose during glycogen metabolism. This mutation represents 20% of GSDI cases.

GSDI is an autosomal recessive disease. So, you should receive the mutated gene from both parents. If your parents are carriers, the incidence of the disease is 25% of pregnancies. 50% of pregnancies are free, and 25% are carriers.

Written by Martin Davis