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Disease Profile

Glycogen storage disease type 4

Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.


US Estimated

Europe Estimated

Age of onset

All ages





Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.


Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.


dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.


Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.


Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other names (AKA)

GSD 4; Andersen disease; Brancher deficiency;


Congenital and Genetic Diseases; Heart Diseases; Nervous System Diseases


Glycogen storage disease type 4 (GSD 4) is part of a group of disorders which lead to abnormal accumulation of glycogen (a storage form of glucose) in various parts of the body. Symptoms of GSD 4 usually begin in infancy and typically include failure to thrive; enlarged liver and spleen (hepatosplenomegaly); and in many cases, progressive liver cirrhosis and liver failure. In rare cases individuals may have a form with non-progressive liver disease, or a severe neuromuscular form. GSD 4 is caused by mutations in the GBE1 gene and is inherited in an autosomal recessive manner. Treatment typically focuses on the specific symptoms that are present in each individual.[1]


The signs and symptoms of glycogen storage disease type 4 (GSD 4) can vary greatly between affected individuals, and several forms of GSD 4 have been described. Most affected individuals have a "classic" form characterized by progressive cirrhosis of the liver, eventually leading to liver failure. In these individuals, signs and symptoms typically begin in infancy and include failure to grow and gain weight appropriately (failure to thrive); enlargement of the liver and spleen (hepatosplenomegaly); abnormal fluid build-up in the abdomen (ascites); and enlargement of veins in the wall of the esophagus (esophageal varices) which may rupture and cause coughing up of blood. Progressive liver disease in affected children can lead to the need for a liver transplant or life-threatening complications by approximately 5 years of age. There have been some reports of affected individuals having nonprogressive liver disease; very mildly affected individuals may not show signs and symptoms of the disease.[1]

There have also been reports of neuromuscular forms of GSD 4, most of which become apparent in late childhood. These may be characterized by skeletal muscle or heart muscle disease (myopathy or cardiomyopathy) caused by the accumulation of glycogen in the muscle tissue. Signs and symptoms in these cases may include muscle weakness or fatigue, exercise intolerance, and muscle wasting (atrophy). Complications with these forms may include heart failure.

A more severe neuromuscular form that is apparent at birth has also been reported; this form may be characterized by generalized edema (swelling cause by fluid); decreased muscle tone (hypotonia); muscle weakness and wasting; joints having fixed positions (contractures); and neurologic involvement, which can cause life-threatening complications early in life.[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
80%-99% of people have these symptoms
Abnormal cardiomyocyte morphology
Abnormal muscle glycogen content
Abnormal neuron branching
Generalized abnormality of skin
Generalised abnormality of skin
Enlarged liver
30%-79% of people have these symptoms
Dilated cardiomyopathy
Stretched and thinned heart muscle
Elevated hepatic transaminase
High liver enzymes
Failure to thrive
Faltering weight
Weight faltering

[ more ]

Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

Low blood albumin
Motor delay
Muscle tissue disease
5%-29% of people have these symptoms
Accumulation of fluid in the abdomen
Scar tissue replaces healthy tissue in the liver
Congestive heart failure
Cardiac failure
Cardiac failures
Heart failure

[ more ]

Esophageal varix
Enlarged vein in esophagus
Fetal akinesia sequence
Flexion contracture
Flexed joint that cannot be straightened
Hepatic failure
Liver failure
Enlarged liver and spleen
Nonimmune hydrops fetalis
High levels of amniotic fluid
Portal hypertension
Prolonged partial thromboplastin time
Prolonged prothrombin time
Respiratory distress
Breathing difficulties
Difficulty breathing

[ more ]

Respiratory insufficiency
Respiratory impairment
Severe muscular hypotonia
Severely decreased muscle tone
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting

[ more ]

Percent of people who have these symptoms is not available through HPO
Arthrogryposis multiplex congenita
Autosomal recessive inheritance
Disease of the heart muscle
Decreased fetal movement
Less than 10 fetal movements in 12 hours
Fluid retention
Water retention

[ more ]

Hydrops fetalis
Muscle weakness
Muscular weakness
Muscular hypotonia
Low or weak muscle tone
Reduced tendon reflexes
Tubulointerstitial fibrosis


Glycogen storage disease type 4 (GSD 4) is caused by mutations in the GBE1 gene. The GBE1 gene normally provides instructions for making the glycogen branching enzyme. This enzyme is necessary for making glycogen, a major source of stored energy in the body. Glycogen is formed by assembling many molecules of glucose. The glycogen branching enzyme is involved in the formation of "branches" of glucose chains, which help to make glycogen more compact for storage and allows it to break down more easily when it is needed for energy. The GBE1 gene mutations that cause GSD 4 lead to a decrease in the amount or functionality of the glycogen branching enzyme. Glycogen is then not formed properly, and substances called polyglucosan bodies build up in cells throughout the body, causing the signs and symptoms of the condition.[2]


Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.


    Management of glycogen storage disease type 4 typically focuses on the signs and symptoms that are present in each individual. Studies have show that in some cases, strict dietary therapy can help to maintain normal levels of glucose in the blood, reduce liver size, reduce symptoms, and allow for improved growth and development. Growing evidence indicates that a highprotein diet may improve muscle function in individuals with weakness or exercise intolerance and slow disease progression. Supportive care is typically needed for complications such as liver failure, heart failure, and neurologic dysfunction. Liver transplantation may be necessary for individuals with progressive liver disease. Individuals with cardiomyopathy may require the use of certain medications.[3][1]


    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference (GHR) contains information on Glycogen storage disease type 4. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Glycogen storage disease type 4. Click on the link to view a sample search on this topic.


          1. Marsden D. Andersen Disease (GSD IV). NORD. 2012; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/394/viewAbstract. Accessed 12/23/2012.
          2. GBE1. Genetics Home Reference. November 2009; https://ghr.nlm.nih.gov/gene/GBE1. Accessed 12/23/2012.
          3. Wayne E Anderson. Glycogen Storage Disease, Type IV Treatment & Management. eMedicine. November 12, 2009; https://emedicine.medscape.com/article/119690-treatment#showall. Accessed 9/8/2011.

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