Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The disease that we will be learning about today is:

Glycogen Storage Disease Type 1A

Also known as von Gierke disease.

What is Glycogen Storage Disease Type 1A?

• Glycogen storage disease type I (also known as GSDI or von Gierke disease) is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body’s cells.
• The accumulation of glycogen in certain organs and tissues, especially the liver, kidneys, and small intestines, impairs their ability to function normally.​
• The overall incidence of GSDI is 1 in 100,000 individuals. GSDIa is more common than GSDIb, accounting for 80 percent of all GSDI cases.
• There are two different subtypes of Type I Glycogen Storage Disease – called type Ia and type Ib.
• Type I Glycogen Storage Disease accounts for about 25% of all cases of GSD diagnosed in the USA and in Europe and has an estimated incidence of about 1 in 100,000 live births.​​
• The treatments of Type I Glycogen Storage Disease are aimed at correcting the metabolic changes in the body and promoting growth and development.​
• The diagnosis of Type I GSD will always include blood studies such as blood glucose, cholesterol, triglycerides, lactate, and uric acid, measurements of growth, and ultrasound or other imaging studies to measure the size of the liver and kidneys.
• A glycogen storage disorder occurs in about one in 20,000 to 25,000 babies. The most common types of GSD are types I, II, III, and IV, with type I being the most common. It is believed that nearly 90% of all patients with GSD have types I through IV. About 25% of patients with GSD are thought to have type I. However, GSD types 0, VI and IX can have very mild symptoms and may be underdiagnosed.​
• Most of the severe forms of GSD are diagnosed in babies and children. Some of the milder types might not be found until the person is an adult.​​

How Do You Get It?

• Type I glycogen storage disease is associated with abnormalities in two genes.​
• Mutations in the G6PC gene result in a deficiency in the glucose-6-phosphatase (G6Pase) enzyme and account for approximately 80% of GSDI.​
• This type of GSDI is termed glycogen storage disease type Ia.
• Type I glycogen storage disease is inherited as an autosomal recessive genetic disorder.
• Molecular genetic testing for the G6PC and SLC37A4 genes is available to confirm a diagnosis.​
• Molecular genetic testing can also be used for carrier testing and prenatal diagnosis. ​

What Are The Symptoms?

• In Type I Glycogen Storage Disease (GSD I), the most frequent first symptoms include an enlarged liver and low blood sugar (hypoglycemia). ​
• After we eat, excess glucose is stored as glycogen mostly in the liver to be used later when we are fasting (not eating for 3-4 hours) to maintain normal glucose levels in our body. ​
• In GSD I the metabolic problem is centered in the liver because the enzyme needed to release glucose from glycogen is missing.
• Individuals with Type I Glycogen Storage Disease are unable to release glucose from glycogen mainly in the liver.​
• They cannot maintain their blood glucose (sugar) levels and within a few hours after eating they will develop hypoglycemia (low blood sugar).
  • The low levels of glucose in the blood of these individuals often result in chronic hunger, fatigue, and irritability. ​
  • These symptoms are especially noticeable in infants. Symptoms of hypoglycemia often appear when the time between feedings increases and the infant sleeps through the night. In infants, children and adults, symptoms may also be present when an illness prevents normal feeding routine and time. If the blood sugar is very low, some individuals may have seizures (hypoglycemic seizures).​
• Other symptoms may include
  • Enlarged kidneys
  • Elevated lactic acid and uric acid
  • Elevated fat levels in the blood
  • Short stature
  • Impeded growth
  • Delayed puberty
  • Gout
  • Decreased bone density
  • Pulmonary hypertension
  • Tumors on the liver (typically not malignant)
  • Kidney disease
    • Proteinuria, kidney stones, hypertension, kidney failure

How Is It Treated?

• Although there has been recent progress in the treatment of GSDIa, including a new dietary product approved by US FDA, there are no drug therapies approved for this disease.
• The treatments of Type I Glycogen Storage Disease are aimed at correcting the metabolic changes in the body and promoting growth and development.​
• Current treatments consist of providing small, frequent feedings during the day. ​
• The primary treatment goal is prevention of hypoglycemia and the secondary metabolic derangements by frequent feedings of foods high in glucose or starch (which is readily digested to glucose).​
• Treatment varies depending on the type of GSD. For types of GSD that involve the liver, treatment is aimed at keeping the right level of glucose in the blood. ​
• This is often enough to maintain the cells fuel needs and prevent long-term complications associated with poorly controlled GSD. Treatment consists of taking regular doses of uncooked cornstarch and/or nutrition supplements. ​
• Cornstarch is a complex carbohydrate that is difficult for the body to digest; therefore it maintains normal blood sugar levels for a longer period of time than most carbohydrates in food. Eating many small meals that are low in sugar can help keep blood sugar levels normal while preventing excess glycogen storage in the liver.​
• Carbohydrate solutions may be given continuously during the night to prevent a drop in blood glucose level during sleep, but this carries more risk of severe hypoglycemia compared to using uncooked cornstarch around the clock.​

Where Can I Learn More???

• Check out our cornerstone on this disease here.
• Learn more about this disease from Association for Glycogen Storage Disease.