National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Glycogen storage disease type 4


Other Names:
GSD 4; Andersen disease; Brancher deficiency; GSD 4; Andersen disease; Brancher deficiency; Amylopectinosis; Glycogen branching enzyme deficiency; Cirrhosis, familial, with deposition of abnormal glycogen; Glycogenosis 4; GSD IV See More
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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]
Last updated: 12/23/2012
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]
Last updated: 9/8/2011

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.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal cardiomyocyte morphology 0031331
Abnormal muscle glycogen content 0012269
Abnormal neuron branching 0500032
Generalized abnormality of skin
Generalised abnormality of skin
0011354
Hepatomegaly
Enlarged liver
0002240
30%-79% of people have these symptoms
Dilated cardiomyopathy
Stretched and thinned heart muscle
0001644
Elevated hepatic transaminase
High liver enzymes
0002910
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Hypoalbuminemia
Low blood albumin
0003073
Motor delay 0001270
Myopathy
Muscle tissue disease
0003198
5%-29% of people have these symptoms
Ascites
Accumulation of fluid in the abdomen
0001541
Cirrhosis
Scar tissue replaces healthy tissue in the liver
0001394
Congestive heart failure
Cardiac failure
Cardiac failures
Heart failure
[ more ] 		0001635
Esophageal varix
Enlarged vein in esophagus
0002040
Fetal akinesia sequence 0001989
Flexion contracture
Flexed joint that cannot be straightened
0001371
Hepatic failure
Liver failure
0001399
Hepatosplenomegaly
Enlarged liver and spleen
0001433
Nonimmune hydrops fetalis 0001790
Polyhydramnios
High levels of amniotic fluid
0001561
Portal hypertension 0001409
Prolonged partial thromboplastin time 0003645
Prolonged prothrombin time 0008151
Respiratory distress
Breathing difficulties
Difficulty breathing
[ more ] 		0002098
Respiratory insufficiency
Respiratory impairment
0002093
Severe muscular hypotonia
Severely decreased muscle tone
0006829
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting
[ more ] 		0003202
Percent of people who have these symptoms is not available through HPO
Arthrogryposis multiplex congenita 0002804
Autosomal recessive inheritance 0000007
Cardiomyopathy
Disease of the heart muscle
0001638
Decreased fetal movement
Less than 10 fetal movements in 12 hours
0001558
Edema
Fluid retention
Water retention
[ more ] 		0000969
Hydrops fetalis 0001789
Muscle weakness
Muscular weakness
0001324
Muscular hypotonia
Low or weak muscle tone
0001252
Reduced tendon reflexes 0001315
Tubulointerstitial fibrosis 0005576
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Last updated: 7/1/2020
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]
Last updated: 12/23/2012
Glycogen storage disease type 4 is inherited in an autosomal recessive manner. This means that an individual must have 2 abnormal copies of the GBE1 gene to be affected (one abnormal copy inherited from each parent). Individuals with one abnormal copy of the GBE1 gene, such as the parents of an affected individual, are referred to as carriers. Carriers typically do not have signs or symptoms of an autosomal recessive condition. When two carriers of an autosomal recessive condition are having children, each of their children has a 25% (1 in 4) risk to be affected, a 50% (1 in 2) risk to be a carrier like each parent, and a 25% chance to not be a carrier and not be affected.
Last updated: 12/23/2012

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 high-protein 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]
Last updated: 9/8/2011

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include galactosemia, hydrops fetalis, and tyrosinemia (see these terms).APBD can also present with or without GBE deficiency indicating that different biochemical defects could result in an identical phenotype.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Glycogen storage disease type 4. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

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

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.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • I was wondering if there is any way for parents that have had a baby with glycogen storage disease type 4 (GSD4) to have a child without this condition. For example, is amniocentesis available or can this be done through in vitro fertilization (IVF)? See answer


  1. Marsden D. Andersen Disease (GSD IV). NORD. 2012; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/394/viewAbstract. Accessed 12/23/2012.
  2. GBE1. Genetics Home Reference. November 2009; http://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; http://emedicine.medscape.com/article/119690-treatment#showall. Accessed 9/8/2011.