What Is Glycogen Storage Disease Type I (GSD I)?

Glycogen storage disease type I (GSD I) is a rare, inherited illness that prevents the body from controlling the amount of glycogen it stores. It is also called von Gierke disease.

People with GSD I have a defect in the amount or the transport of the enzyme that changes glycogen into glucose. Having this disease can let too much glycogen stay in the liver and kidneys. The buildup of glycogen can also affect muscles and other organs.

GSD I is often found by the time a child is 6 months old. The first signs often occur as hypoglycemia (dangerously low blood sugar).

While changes in diet may help to improve the outcomes of this illness, there is no treatment. Having it can lead to severe, long-term health problems.

This article describes GSD I symptoms, causes, diagnosis, and treatment.

Types of GSD I

GSD I is one of 16 recognized types of glycogen storage diseases that interfere with the way your body changes glycogen into glucose. This process is necessary to allow your body to provide glucose for energy and for steady glucose levels.

There are two variations of GSD I. About 80% of people with GSD I have glycogen storage disease type Ia (GSD Ia), while glycogen storage disease type Ib (GSD Ib) affects the remaining 20%.

GSD Ia involves insufficient levels or the absence of the glucose-6-phosphatase (G6Pase) enzyme. This enzyme converts glycogen into glucose so it can be circulated to the rest of the body.

GSD Ib involves normal activity levels of the G6Pase enzyme, but a deficiency of glucose-6-phosphate translocase (G6PT), the transporter enzyme that carries glucose to the rest of the body. This results in a dangerous accumulation of glycogen in the liver and kidneys.

Symptoms

Symptoms of GSD I vary by individual and the variety of disease that is involved. The type of symptoms that occur also varies with age.

Symptoms occur when too much glycogen and fat remain stored within a cell, rather than being released as glucose. This can damage cells, resulting in problems in the liver, kidneys, and other organs throughout the body.

During the newborn and infant phase, GSD I can cause the following symptoms:

• Hypoglycemia
• Hepatomegaly (enlarged liver)
• Lactic acidosis
• Hyperuricemia (high uric acid levels)
• Hyperlipidemia (high levels of lipids in the blood, such as cholesterol and triglycerides)
• Hypoglycemic seizures
• Protruding abdomen

While hypoglycemia is more common during the newborn phase, symptoms may not appear until the child is 3 to 6 months old, when there are longer gaps between feedings. During these fasting periods, the disease interferes with the body's ability to provide glucose to the rest of the body.

During childhood and into adulthood, GSD I can include the following symptoms, which are more likely to occur when the condition is untreated:

• Full cheeks and round face
• Short stature
• Delayed motor development
• Abnormal cognitive development from recurrent hypoglycemic episodes
• Thin extremities
  
• Delayed puberty
  

Causes

GSD I occurs through heredity. It is an autosomal recessive disease, meaning the child inherits one copy of a mutated gene from each parent. An autosomal gene is located on a numbered chromosome.

When a parent has a healthy dominant gene and a defective recessive gene for GSD I, they usually don't get it because their dominant gene is healthy. However, if they conceive a baby with a partner who also has a defective recessive gene variant, their baby has a stronger chance of receiving two defective recessive genes and no healthy genes. When that occurs, the baby develops the disease.

GSD I is relatively rare. It occurs in about 1 in 100,000 births, affecting males and females equally. The incidence is much higher in Ashkenazi Jews, who are affected at the rate of 1 in 20,000 births.

Diagnosis

To get a GSD I diagnosis, you will need to be examined by a healthcare provider. Based on a physical assessment and history of symptoms, the provider can determine the laboratory tests needed to help determine a diagnosis.

If your healthcare provider suspects GSD I, they may order blood and urine tests. They will evaluate levels of the following substances to determine whether there is abnormal activity:

• Glucose
• Lactate
• Uric acid
• Triglycerides
• Cholesterol

While a biopsy of the liver can confirm the diagnosis, it is considered unnecessary unless there is evidence of an enlarged liver.

Instead of having an invasive biopsy, most people can receive molecular genetic testing to accurately determine whether the genes that trigger this condition are abnormal. This type of testing can also identify carriers and a prenatal diagnosis. Exome sequencing, a type of genetic testing that identifies changes in your genes, can also be used to diagnose this disease.

Treatment

There is no proven treatment or cure for GSD I. However, the disease can be managed with dietary therapy. This requires following special diet designed to keep glucose levels normal, avoid hypoglycemia, and promote normal growth and development.

Infants are fed soy-based, sugar-free formula on demand every two to three hours. As the infant sleeps longer, they must be awakened every three to four hours for feeding and blood glucose monitoring.

Depending on the child's condition and their healthcare provider's advice, dietary changes to manage this disease can include the following:

• A diet in which carbohydrates make up 60% to 70% of calories
• Frequent small servings of carbohydrates consumed during the day and night
• Supplements of calcium, vitamin D, and/or iron
• Frequent servings of uncooked cornstarch, a slow-release carbohydrate, to improve and support blood glucose levels
• Avoidance of fructose and sucrose with limited intake of lactase and galactose
• Allopurinol, a drug that reduces uric acid in the blood
• Medications to lower lipid levels and/or treat kidney conditions
• Human granulocyte colony-stimulating factor (GCSF) to treat infections in type Ib

These dietary changes are intended to prevent acute and long-term complications, achieve normal psychological development, and improve quality of life. They must be maintained throughout an affected person's lifetime to benefit from their effects on the disease.

Prognosis

Early diagnosis and treatment with dietary therapy can help people who have GSD I experience normal growth and puberty. Making advised dietary changes can also prevent hypoglycemia and other symptoms and improve life expectancy.

Many people who have this disease enjoy normal lifestyles and live into adulthood. People with this condition also have successful pregnancies and childbirths.

Treating the condition and maintaining ongoing monitoring can help reduce the risk of developing the following complications:

• Bleeding disorders from damaged platelet function
• Kidney diseases
• Osteoporosis
• Xanthomatosis (a skin condition)
• Diarrhea
• Recurring bacterial infections due to neutropenia (in type Ib only)
• Gout
• High blood pressure (hypertension)
• Pulmonary hypertension
• Noncancerous liver tumors with the potential for transformation into cancer
• Polycystic ovary syndrome (PCOS)
• Heavy menstrual bleeding
• Enterocolitis (inflammation in the digestive tract)
• Hypothyroidism
• Acute pancreatitis
• Early atherosclerosis
• Increased mouth ulcers

Coping

Successful management of GSD I includes ongoing care and monitoring by a metabolic team. This typically includes the following healthcare professionals:

• Primary healthcare provider
• Metabolic specialist
• Metabolic dietitian
• Hepatologist
• Gastrointestinal specialist
• Social worker
• Genetic counselor
• Psychologist

Having this condition also requires home blood glucose monitoring using a glucometer or continuous glucose monitoring to assess for hypoglycemia and hyperglycemia.

Genetic counseling is advised for parents of an affected child, because siblings of an affected child have a 25% chance of having the disease. They also have a 50% chance of being an asymptomatic carrier.

Summary

GSD I causes problems with the body's ability to control the amount of glycogen it stores. It is often found in infants by 6 months of age, when symptoms of hypoglycemia occur.

This disease allows too much glycogen to remain in the liver and kidneys. It also prevents the release of glucose to the rest of the body. The result harms cells and raises the risk of organ and tissue problems in the rest of the body.

While there is no proven treatment or cure for this condition, dietary changes and glucose monitoring can improve outcomes. These steps can aid in quality of life, extend the length of life, and reduce the risk of other health problems.

A Word From Verywell

Early diagnosis and treatment have improved the prognosis and outcomes for people with GSD I.

This disease can be managed with the support of a specialized healthcare team. Lifetime dietary therapy and glucose monitoring can help you achieve the best outcomes for you or your affected child.

Educating yourself and your affected children about the condition and dietary restrictions can reduce early symptoms and the risk of complications. While no medical treatment exists, gene therapies in mice models have shown promising results for the potential of future trials in humans.