Function of Glycogenesis in Glycogen Storage Disease

Glycogenesis is a process your body uses to convert the glucose (sugar) you eat into glycogen, which is then stored in your liver and burned later for energy. It happens whenever you take in more glucose than your body needs right away. 

Then, when you need the energy, your body creates it by taking glycogen out of storage and breaking it down. 

Glycogen storage disease (GSD) is a rare condition found almost exclusively in babies and young children. Their bodies can’t store or break down glycogen because they don’t have the right enzymes for the process. This can lead to problems with their:

• Liver and other organs
• Skeletal muscles
• Blood glucose regulation
• Growth and development

This article explores the process of glycogenesis, what your genetics has to do with it, and the various types of GSD.

What Is Glycogenesis?

The cells in your body need a constant supply of energy to fuel the processes that keep you alive and healthy. Its preferred form of energy comes from glucose, which is a simple sugar that’s easy to convert to glycogen.

If you need energy right away, your body uses the glucose you just ate. But any excess glucose is converted to glycogen and stored in your liver and muscle cells.

When your blood glucose levels dip, as they often do between meals or overnight, your body takes glycogen out of the liver and muscles and converts it back into glucose for easy use. This process is called glycogenolysis.

Breaking down glycogen for energy is different from breaking down fat, which is a slower process. Glycogen is stored as a carbohydrate, not a fat. Fat stores are used for long-term energy, while glucose is used for quick energy.

The processes of glycogenesis, glycogen storage, and its conversion back to glucose rely on several enzymes (substances that trigger chemical reactions). People with GSD lack a necessary enzyme.

Hereditary Aspect of Glycogen Synthesis

Glycogen storage disease is hereditary, meaning parents pass it to their children through their genes. It’s also recessive, which means it requires a gene from each parent to result in GSD.

The parents often do not know that they carry the mutated gene until their child is diagnosed with GSD.

Common Types of Glycogen Storage Diseases

Most GSD is diagnosed before the first birthday, but sometimes it's not apparent until later in childhood. Symptoms often develop when a baby is about 3 or 4 months old. They may include:

• Poor growth (failure to thrive)
• Low blood glucose levels (hypoglycemia), which may lead to seizures
• Enlarged liver and/or kidneys
• Poor muscle tone
• Muscle pain and cramps while exercising
• Overly acidic blood (acidosis)
• Fatigue

GSD can take one of many forms, depending on which glycogenesis enzyme the body doesn’t produce and what it affects. The most common are types are I, II, III, and IV, as follows:

• Type I (von Gierke disease): The most common form; has subgroups Ia and Ib; lacks the enzyme glucose-6-phosphatase α (alpha) or glucose-6-phosphate transporter; affects the liver, kidneys, intestines, and sometimes blood cells
• Type II (Pompe disease): Lacks enzyme acid α-glucosidase; affects the muscles, heart, liver, nervous system, and blood vessels
• Type III (Forbes-Cori disease): Lacks enzyme glycogen debranching enzyme; affects the liver, heart, skeletal muscles, and blood cells
• Type IV (Andersen disease): Lacks enzyme glycogen debranching enzyme; affects the liver, brain, heart, muscles, skin, and nervous system

These types make up about 90% of GSD cases. Subtypes of GSD include:

Rarer Types

Less common types of GSD make up the other 10% of cases, so each type is quite rare, as follows:

• Type 0 (Lewis’s disease): Lacks liver glycogen synthase and affects the liver (type 0a); lacks muscle glycogen synthase and affects the muscles (type 0b)
• Type V (McArdle’s disease): Lacks muscle glycogen phosphorylase; affects skeletal muscles
• Type VI (Hers disease): Lacks enzyme liver glycogen phosphorylase; affects the liver and blood cells
• Type VII (Tarui’s disease): Lacks muscle phosphoglucose kinase; affects skeletal muscles and blood cells
• Type IX (phosphorylase kinase deficiency): Lacks phosphorylase kinase; affects the liver
• Type XI (Fanconi-Bickel syndrome): Lacks glucose transporter 2; affects the liver, kidneys, and intestines
• Type XII: Lacks aldolase A; affects the blood cells, liver, and muscles
• Type XIII: Lacks ß (beta)-enolase; affects the muscles, heart, nervous system, and kidneys
• Type XV: Lacks glycogenin-1; affects the muscles, heart, and nervous system

Types VI and IX can be mild enough that they’re not diagnosed until adulthood.

Summary

Glycogenesis is the process your body uses to turn glucose (sugar) from food into glycogen, which is stored as a carbohydrate in your liver and muscle cells. It can be quickly broken down for energy later on. 

Glycogenesis only occurs when your cells have more glucose than they need. The process of glycogenesis, retrieval from cells, and conversion into energy involves multiple enzymes. 

Glycogen storage disease is a rare hereditary condition primarily in babies and young children that can impair development. It’s caused by both parents passing on a mutated gene. 

GSD is divided into several types depending on which enzyme is missing and which organs and systems it affects.

A Word From Verywell

If you’re wondering about GSD in your baby or toddler, you're likely afraid. Rest assured that the condition is manageable. 

Treatment primarily involves a special diet to keep blood sugar levels in a healthy range and, depending on the type of GSD, nutritional supplements and/or medications to prevent or manage complications.

Work with your pediatrician to learn about your child’s condition and take steps to manage it. This will help your child to feel better, grow, and thrive.