What Is Glycogen Storage Disease Type 0 (GSD 0)?

Glycogen storage disease type 0 (GSD 0) is a rare genetic disease that prevents the normal use and storage of glycogen. Glycogen is the stored form of glucose (blood sugar).

This disease causes slightly lower than normal levels of stored glycogen in the muscles or liver. It varies from other glycogen storage disorders, which cause the storage of too much glycogen.

People with this disease have a deficiency of an enzyme called glycogen synthase (GSY) due to a genetic defect. This enzyme helps the body produce and store glycogen. Without the right amount of this enzyme, the body can't maintain enough glycogen to support normal function.

The first signs of GSD 0 often appear in older infants when nighttime feedings stop. During this time of fasting, blood sugar levels drop. Hypoglycemia, or low blood sugar, can result.

Though there is no cure, a diet that avoids fasting and the risk of low blood sugar can often manage this disease. Finding the problem and starting the right diet early in life can support the best outcomes.

This article describes GSD 0 symptoms, causes, diagnosis, and treatment.

Types of GSD 0

GSD 0 is one of 16 types of recognized glycogen storage diseases that interfere with the processes needed to change glycogen to glucose.

There are two types of GSD 0. These types vary based on the organ where the enzyme defect exists:

• Liver GSD 0 (due to deficiency of liver glycogen synthase)
• Muscle GSD 0 (due to deficiency of muscle and heart glycogen synthase)

Symptoms

Symptoms of glycogen storage disease can vary by individual and type.

Liver GSD 0 usually causes symptoms after the newborn stage when babies begin sleeping through the night and no longer awaken for nighttime feedings. In healthy babies, stored glycogen releases glucose that tissues need to use during sleep. However, because this disorder interferes with normal levels of glycogen, this isn't always possible for affected babies.

After sleeping, babies with GSD 0 may have the following short-term signs of hypoglycemia as a result of fasting for a long period:

• Lethargy
• Apathy
• Jitteriness
• Diaphoresis
• Tachycardia
• Dysarthria
• Hypotonia
• Ataxia
• Sweating
• Pallor
• Nausea and vomiting
• Ketosis
• Seizures

Because these signs are often mild, they may go unnoticed for years, leaving the affected child undiagnosed. Long-term damage, including growth failure and developmental delay, can occur if these symptoms become severe and remain untreated.

Muscle GSD 0 usually appears in early childhood. It interferes with the heart's ability to pump effectively and can include the following symptoms, especially after moderate physical activity:

• Muscle pain
• Weakness
• Fainting
• Decreased level of consciousness for up to a few hours
• Heart arrhythmia

Muscle GSD 0 also increases the risk of cardiac arrest and sudden death, especially after physical activity.

Causes

GSD 0 is an inherited disorder. It is passed from parent to child in an autosomal recessive pattern. This means that both parents must pass the same defective gene for the child to develop a disorder.

When a parent has an autosomal recessive trait, they don't have symptoms and usually don't know they have it. However, if they have a child with a partner who also has a recessive gene for the disorder, their children have a 25% chance of getting the disease.

Defects in the glycogen synthase 1 (GYS 1) gene cause muscle GSD 0, while defects in the glycogen synthase 2 (GYS 2) gene cause the version of the disorder that affects the liver.

Diagnosis

Only a healthcare provider can deliver an accurate diagnosis of GSD 0. The diagnosis involves a physical examination, a history of symptoms, and the laboratory tests needed to identify the disorder.

Laboratory tests usually involve an evaluation of the following substance levels to identify whether they reflect levels that are unique to this disease:

• Glucose
• Lactate
• Uric acid
• Cholesterol
• Triglycerides
  

Patients who have a suspected case of GSD 0 are usually admitted for inpatient monitoring after fasting. A glucagon challenge test, which measures the amount of glucagon in the blood, may also be recommended.

A liver biopsy can accurately diagnose this disease. However, molecular genetic testing to identify abnormal genes can often prevent the need for an invasive procedure. This type of testing can also specify carriers and a prenatal diagnosis.

Exome sequencing, a type of genetic testing that identifies changes in your genes, can also diagnose GSD 0.

Treatment

Though there is no proven medical treatment or cure for GSD 0, dietary therapy can manage the disorder. This involves a diet organized to avoid low blood sugar by avoiding fasting. It is also designed to provide enough calories and protein for normal growth and development.

Frequent meals and snacks throughout the day can help maintain normal blood sugar levels. Eating a diet high in protein may help offset common symptoms of cramping, fatigue, and lethargy. Uncooked cornstarch can prevent overnight hypoglycemia during sleep because it delivers a "slow release" type of glucose.

The recommended diet involves avoiding highly processed carbohydrates that prevent the changing of excess glucose into lactate, or lactic acid.

Prognosis

GSD 0 usually involves a good prognosis for normal growth, intellectual development, and average lifespan. Early diagnosis and treatment with dietary management can prevent hypoglycemic episodes and support this prognosis.

Short-term symptoms of liver GSD 0 can improve when food is consumed. However, in cases in which symptoms remain undiagnosed for years, the disease may lead to growth failure and developmental delay.

Muscle GSD 0 can interfere with the heart's ability to pump blood effectively. This increases the risk of cardiac arrest and sudden death after physical activity for children and adolescents with this version of the disease.

Coping

Patient education for the affected person, their parents, and sibling(s) can help those involved understand how to better manage the disease, as well as their risk of inheriting or passing it on to their children.

Managing this disease usually involves lifelong monitoring and working with a team of specialists that may include the following healthcare professionals:

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

Summary

GSD 0 hinders the body's power to produce, use, and store glycogen. People with this disease have a deficiency of the glycogen synthase enzyme (GSY) in either their liver or muscles. The disease is passed from parent to child.

Though other glycogen storage disorders result in too much glycogen, this type causes slightly lower than normal levels in the liver or muscles. When levels of this enzyme are low, the body can't supply glucose to the rest of the body and support normal function.

This lifetime disease is often found in older infants or young children based on whether the liver or muscles are affected. Hypoglycemia, or low blood sugar, is a common first symptom.

This disease has no cure but can be controlled with the right diet. The key to getting the best outcomes is to find the disease early. This can allow the affected child to start a diet that prevents bouts of low blood sugar before it affects normal growth and development.

A Word From Verywell

Though it can be challenging to follow the diet necessary to manage this condition, doing so increases your chances of achieving the best possible outcomes. Having a multidisciplinary healthcare team can help ensure that you're doing all you can to live a normal life.

This and other glucose storage diseases are passed from parents to their children. If your parents or a sibling has one of these diseases, it's important that you learn about your risk of passing it on to your children so you make the best decisions for your life.