ConditionHormones & metabolism
Glycogen Storage Disease
Glycogen storage disease (GSD) is a group of rare inherited conditions in which an enzyme needed to make or break down glycogen, the body's stored form of sugar, is missing or faulty. Depending on the type, it mainly affects the liver, causing low blood sugar, an enlarged liver and poor growth, or the muscles, causing exercise intolerance, cramps and weakness, and sometimes the heart. Treatment depends on the type and often centers on frequent feeding with cornstarch, while Pompe disease has enzyme replacement therapy.
Also called: GSD, glycogenosis, glycogen storage disorders
At a glance
- What it is
- Inherited enzyme deficiencies that disrupt glycogen storage or breakdown.
- How common
- About 1 in 20,000 to 40,000 births combined.
- Liver types
- Low blood sugar between meals, enlarged liver, poor growth (types I, III, VI, IX).
- Muscle types
- Exercise intolerance, cramps, dark urine after exercise, weakness (types V, VII, II).
- Treatment
- Frequent meals and cornstarch, diet adjustments, enzyme replacement for Pompe disease.
When to get help
Call 911 or go to the ER
- Seizures, unresponsiveness or extreme drowsiness in a child with GSD, especially after missing a meal or feed (possible severe low blood sugar)
- Dark, cola-colored urine with severe muscle pain and weakness after exercise (possible rhabdomyolysis)
- A floppy infant with breathing or feeding difficulty (possible Pompe disease)
See a doctor within a day or two
- Vomiting or illness that prevents a child with liver GSD from eating or keeping cornstarch down
- Fast breathing, lethargy or vomiting (possible lactic acidosis)
Book a routine appointment
- A baby or child with a swollen belly, enlarged liver, poor growth or frequent low blood sugar
- Muscle cramps or fatigue within minutes of exercise, especially with a "second wind"
- Progressive muscle weakness in a child or adult
How glycogen works
After a meal, the body stores extra glucose as glycogen in the liver and muscles. Between meals, the liver breaks glycogen down to keep blood sugar steady, while muscles use their glycogen for fuel during activity. Each GSD type affects a different enzyme in these pathways, so glycogen either cannot be released properly or builds up abnormally in tissues.
Main types
| Type | Name | Enzyme | Main organs | Key features |
|---|---|---|---|---|
| Ia, Ib | Von Gierke disease | Glucose-6-phosphatase (or transporter) | Liver, kidney | Severe fasting low blood sugar, large liver, high lactate, uric acid and fats, short stature; Ib also low neutrophils and infections |
| II | Pompe disease | Acid alpha-glucosidase | Muscles, heart | Infant form: floppy baby, enlarged heart; late-onset: progressive muscle and breathing weakness |
| III | Cori disease | Debranching enzyme | Liver, muscle, heart | Large liver, milder low blood sugar, later muscle weakness and cardiomyopathy |
| IV | Andersen disease | Branching enzyme | Liver, nerves | Liver cirrhosis in early childhood |
| V | McArdle disease | Muscle phosphorylase | Muscle | Exercise intolerance, cramps, "second wind", dark urine. See McArdle disease |
| VI, IX | Hers disease, phosphorylase kinase deficiency | Liver phosphorylase or its activator | Liver | Usually milder: large liver, mild low blood sugar, often improves with age |
| VII | Tarui disease | Muscle phosphofructokinase | Muscle, red cells | Exercise intolerance, hemolysis |
Symptoms
Liver forms
- low blood sugar after short fasts, causing irritability, sweating, shakiness or seizures
- a swollen belly from an enlarged liver
- poor growth and delayed puberty
- "doll-like" round face
- easy bruising and nosebleeds (type I)
- frequent infections and mouth ulcers (type Ib)
Muscle forms
- muscle cramps, pain and fatigue during exercise
- dark urine after intense exercise from muscle breakdown (rhabdomyolysis)
- progressive weakness, including breathing muscles (Pompe)
- cardiomyopathy in Pompe and some type III patients
Inheritance
Most types are autosomal recessive: a child inherits a faulty gene from each parent. One form of type IX is X-linked, mainly affecting boys.
Diagnosis
- Blood tests: glucose, lactate, uric acid, cholesterol and triglycerides, liver enzymes, creatine kinase (CK)
- Genetic testing: now the main way to confirm the type
- Enzyme activity tests on blood, skin or tissue
- Liver or muscle biopsy in some cases
- Newborn screening: Pompe disease is on the US recommended newborn screening panel
- Forearm exercise test and imaging for muscle types
- Echocardiogram for heart involvement
Treatment
Liver forms
- frequent feeds and meals every 2 to 4 hours, including overnight in infants
- uncooked cornstarch, which releases glucose slowly, given every few hours and at bedtime
- continuous overnight tube feeds for some young children
- limiting fructose and galactose in type I
- medicines for high uric acid, high lipids and kidney protection
- granulocyte colony-stimulating factor and empagliflozin for low neutrophil counts in type Ib
- monitoring for liver adenomas and, in some types, liver cancer
- liver transplant for severe or complicated cases
Muscle forms
- moderate, regular aerobic exercise with gradual warm-up, avoiding sudden intense effort
- sugar or a sports drink before exercise may help in McArdle disease
- avoiding statins and other drugs that can damage muscle when possible
Pompe disease
Enzyme replacement therapy (alglucosidase alfa, avalglucosidase alfa, or cipaglucosidase alfa with miglustat) given by IV infusion every 2 weeks improves survival and function. Respiratory support and physical therapy are also important.
Outlook
With modern management, many people with liver GSDs reach adulthood with good quality of life, although long-term complications such as kidney disease and liver adenomas need monitoring. Muscle forms vary from mild exercise limitation to progressive disability. Early diagnosis and treatment of Pompe disease, especially the infantile form, are critical.
Frequently asked questions
What is glycogen storage disease?
It is a group of inherited conditions in which the body cannot properly store or break down glycogen, the stored form of glucose. Depending on the type, it causes low blood sugar and liver enlargement, muscle problems, or heart problems.
What are the most common types of glycogen storage disease?
Type I (von Gierke disease), type II (Pompe disease), type III (Cori disease), type V (McArdle disease) and types VI and IX are among the most commonly diagnosed. Type IX is one of the most frequent liver forms and is often mild.
How is glycogen storage disease treated?
Liver forms are managed with frequent meals, uncooked cornstarch to prevent low blood sugar, and diet changes. Muscle forms are managed with careful exercise. Pompe disease is treated with enzyme replacement therapy. A metabolic specialist and dietitian guide care.
Can adults have glycogen storage disease?
Yes. Some types, such as McArdle disease and late-onset Pompe disease, may not be diagnosed until adulthood. People with childhood-onset types also live into adulthood and need ongoing specialist follow-up.
Sources
This guide was written from current patient and clinical guidance, including:
- American College of Medical Genetics and Genomics: Diagnosis and management of glycogen storage disease type I
- National Organization for Rare Disorders: Glycogen storage diseases
- MedlinePlus Genetics: Glycogen storage disease type I; Pompe disease
- Association for Glycogen Storage Disease: GSD types
- Genetic and Rare Diseases Information Center (GARD): Glycogen storage disease