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

Glycogen storage disease type IV (GSD IV) is a rare disorder that results in the formation of damaged glycogen. Glycogen is the form of glucose that is stored in the liver and muscles.

This condition, also known as Andersen disease, is caused by a defect in the glycogen-branching enzyme (GBE1). This enzyme promotes the process by which glycogen changes to glucose.

Without the change into glucose, the impaired glycogen stays in the liver and other organs. Problems result when the body misidentifies it as a foreign substance. This promotes a reaction from the immune system, which can result in organ damage.

There are five types of GSD IV, which vary in their symptoms and severity. The disease types differ based on the amount of bad glycogen in the body. There are no proven treatments for any type of glycogen storage disease.

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

Illustration of a human liver

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Types of GSD IV

GSD IV is one of 16 types of recognized varieties of glycogen storage disease. These conditions interfere with the processes needed to change glycogen to glucose.

There are five types of GSD IV. These varieties differ greatly in their onset, progression, treatment, and prognosis and include:

  • Perinatal neuromuscular type (most severe)
  • Congenital (at or before birth) muscular type
  • Progressive hepatic (relating to the liver) type (also known as classic type, the most common form)
  • Nonprogressive hepatic type
  • Childhood neuromuscular type

Frequency of GSD IV

GSD IV is an extremely rare condition. It affects 1 in 600,000 to 800,000 people in the world. This represents about 3% of all people with glycogen storage disease.

Symptoms

Symptoms are based on the type of GSD IV present and can impact each person differently.

The liver, muscles, heart, nervous system, and other bodily tissues can be affected in all types of GSD IV. Most varieties of this disease involve muscle weakness and cramps.

Perinatal neuromuscular type

Perinatal neuromuscular type develops before birth and has the most severe impact. Common symptoms include:

  • Excess fluid accumulation in and around the body of the fetus (polyhydramnios)
  • Decrease in fetal movement
  • Joint stiffness after birth (arthrogryposis)
  • Severe hypotonia (decreased muscle tone) after birth
  • Severe atrophy (wasting away of tissue) after birth
  • Weakened heart and breathing muscles

Congenital muscular type

Congenital muscular type develops in early infancy. Common symptoms include:

  • Severe hypotonia, affecting breathing muscles
  • Dilated cardiomyopathy (heart muscle disease that makes it harder for the heart to pump blood)
  • Enlarged and weakened heart

Progressive hepatic type

Progressive hepatic type is the most common type of GSD IV. Symptoms begin within the first months of life and include the following characteristics:

Nonprogressive hepatic type

Nonprogressive hepatic type is a less severe form of hepatic type that doesn't involve cirrhosis of the liver. Symptoms appear in early childhood and include the following characteristics:

  • Hepatomegaly
  • Liver disease
  • Hypotonia
  • Myopathy (muscle weakness)

Childhood neuromuscular type

Childhood neuromuscular type occurs in late childhood with a wide range of severity. Symptoms can include:

  • Myopathy
  • Dilated cardiomyopathy
  • Mild to severe muscle weakness

Causes

GSD IV is a genetic disorder. It is inherited in an autosomal recessive pattern. This means that both parents are required to have the same defective gene in order to pass it on to their child. The disease is passed on one of the autosomal or numbered chromosomes.

People who carry an autosomal recessive trait don't have symptoms of the disease. However, they can pass it on to their child if the child's other parent has the same autosomal recessive trait. Their children have a 25% chance of getting the disease when these circumstances occur.

Defects in the GBE1 gene cause GSD IV. The severity of the disease depends on the amount of defective versus functional glycogen that is produced. The most severe varieties of this disease produce less than 5% of functional GBE1.

Diagnosis

There is no specific diagnostic test for GSD IV. Most people with this disease are diagnosed during infancy or childhood, though some people may not be diagnosed until adulthood.

A diagnosis of this disease requires one or more laboratory tests that identify certain abnormalities common with this disorder. This includes the following tests:

Treatment

With so much variation in symptoms and progression of GSD IV, there is no standard treatment. Treatment is based on addressing each individual's symptoms. Currently, there is no cure for GSD IV.

Like other glycogen storage diseases, treatment for this condition usually involves following a specific diet to maintain normal levels of glucose in the blood and improve liver function and muscular strength.

Liver transplantation for the treatment of progressive liver failure has been effective for some patients. Heart transplantation may be necessary when heart damage is severe.

Medication may be necessary to treat heart conditions like cardiomyopathy. Physical therapy can help counter the effects of muscle symptoms like myopathy or hypertonia.

Prognosis

GSD IV is a progressive disease in which the liver, muscles, and heart experience increasing damage. The prognosis differs based on the variety of this disease and its progression. Generally, the later onset of the disease aligns with less severe variations and better outcomes.

Without a liver transplant, the perinatal neuromuscular and progressive hepatic types of GSD IV have poor prognoses. Severe liver failure often results in death within the first five years of life.

Coping

Managing GSD IV and its symptoms requires lifelong monitoring. This involves working with a multidisciplinary team that may include the following healthcare professionals:

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

If you, your child, or a sibling has this disease, genetic counseling can help you understand your risk of passing it on to your children.

Summary

GSD IV describes a group of disorders that result in the formation of damaged glycogen.

This disease is caused by a defect in the glycogen branching enzyme (GBE1). This interferes with the normal transformation of glycogen into glucose. As a result, the damaged glycogen stays in the liver and other organs. Liver damage is a common result.

There are five varieties or subtypes of this disease, which can vary greatly in symptoms and outcomes. These subtypes vary based on the amount of bad glycogen in the body.

There are no proven treatments for any type of glycogen storage disease, but diet can help with disease management. However, when severe liver damage occurs, a liver transplant may be the only way to prevent death.

A Word From Verywell

Being the parent of a child with GSD IV can be devastating because of the poor outcomes that often accompany this diagnosis. It can also be lonely dealing with this condition as a parent or patient because the condition is so rare. Family and friends may not understand the disease or the challenges that it brings.

You may find help from online or in-person support groups for people with glycogen storage diseases. This can help offset feelings of isolation and frustration that are common when dealing with a rare disease. These groups can often be a source of emotional support, as well as a resource for sharing disease management strategies.

Frequently Asked Questions

  • Is GSD IV preventable?

    No. GSD IV can't be prevented because it is an inherited disease. If you have a family member with this disease, genetic testing can determine your risk factors for developing this disease and passing it to your child. It's important to remember that the presence of a defective gene doesn't always mean that the disease will develop.

  • What are common complications of GSD IV?

    GSD IV can cause liver damage so severe that a liver transplant is necessary. Heart failure, breathing problems, and nervous system issues can also occur. Muscle wasting and poor muscle tone can complicate heart and breathing function.

  • What is the least severe form of GSD IV?

    The nonprogressive type often has the least severe symptoms. This variety of the disease usually doesn't involve cirrhosis of the liver, a life-threatening problem that occurs with other types. Additionally, the prognosis is better among people who are diagnosed later in life with any type.

4 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Ross KM, Ferrecchia IA, Dahlberg KR, Dambska M, Ryan PT, Weinstein DA. Dietary management of the glycogen storage diseases: evolution of treatment and ongoing controversiesAdv Nutr. 2020;11(2):439-446. doi:10.1093/advances/nmz092

  2. MedlinePlus. Glycogen storage disease type IV.

  3. NORD - National Organization for Rare Disorders, Inc. Andersen Disease (GSD IV).

  4. Medscape. Type IV Glycogen Storage Disease.

By Anna Giorgi
Anna Zernone Giorgi is a writer who specializes in health and lifestyle topics. Her experience includes over 25 years of writing on health and wellness-related subjects for consumers and medical professionals, in addition to holding positions in healthcare communications.