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 2

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Other Names:
Pompe disease; Acid maltase deficiency disease; Aglucosidase alfa; Pompe disease; Acid maltase deficiency disease; Aglucosidase alfa; Alpha-1,4-glucosidase deficiency; Cardiomegalia glycogenica diffusa; Deficiency of alpha-glucosidase; GSD II; Deficiency of lysosomal alpha-glucosidase See More
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Glycogen storage disease type 2, also known as Pompe disease or acid maltase deficiency disease, is an inherited metabolic disorder.[1][2][3] While glycogen storage disease type 2 is a single disease, it may be classified in 2 forms according to the rates of disease progression, its severity and the age at which symptoms start. The classic infantile-onset starts before 12 month of age and involves the heart muscle (myocardiopathy). The later-onset form may start before 12 months of age (non-classic infantile-onset), or after 12 months of age, but does not affect the heart. Muscle weakness is a main symptom in all forms. The infantile-onset is the most severe form and, if untreated, it may lead to death from heart failure in the first year of life. The late-onset form is usually milder, but if untreated may lead to severe breathing problems.[1][4] 

Glycogen storage disease type 2 is caused by variants (mutations) in the GAA gene which have instructions to produce the enzyme acid alpha-glucosidase (acid maltase), needed to break down glycogen, a substance that is a source of energy for the body. The enzyme deficiency results in the accumulation of glycogen inside lysosomes, structures within cells that break down waste products within the cell. Accumulation of glycogen in certain tissues, especially muscles, impairs their function.[1][2][3]

In 2006, the U.S. Food and Drug Administration (FDA) approved the enzyme replacement therapy Myozyme as a treatment for all patients with glycogen storage disease type 2. Another similar drug called Lumizyme has recently been approved for the treatment this disease.[1][3][5] Additional treatment of Pompe disease is symptomatic and supportive and may include respiratory and feeding support and physical therapy.[1]
 
Last updated: 6/1/2018
The classic infantile form of glycogen storage disease type 2 is characterized by severe muscle weakness (myopathy) and abnormally diminished muscle tone (hypotonia) without muscle wasting, and usually manifests within the first few months of life. Additional abnormalities may include enlargement of the heart (cardiomegaly), the liver (hepatomegaly), and/or the tongue (macroglossia).[1] Affected infants may also have poor feeding, failure to gain weight and grow at the expected rate (failure to thrive), breathing problems, and hearing loss. Most infants with glycogen storage disease type 2 cannot hold up their heads or move normally. [2] Without treatment, progressive cardiac failure usually causes life-threatening complications by the age of 12 to 18 months.[1][2]

The non-classic infantile form of glycogen storage disease type 2 usually presents within the first year of life. Initial symptoms may include delayed motor skills (crawling, sitting) and myopathy. Cardiomegaly may be present, but unlike the classic infantile form, cardiac failure does not typically occur. Muscle weakness may lead to serious, life-compromising breathing problems by early childhood.[2][4]

In the late onset form of glycogen storage disease type 2, symptoms may not be evident until childhood, adolescence, or adulthood. This form is usually milder than the infantile-onset form of the disorder. Most individuals experience progressive muscle weakness, especially in the legs and the trunk, including the muscles that control breathing.[2]
Last updated: 6/20/2016

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
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HPO ID
80%-99% of people have these symptoms
Abdominal wall muscle weakness 0009023
Cardiomegaly
Enlarged heart
Increased heart size
[ more ] 		0001640
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment
[ more ] 		0100543
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty
[ more ] 		0002015
Dysphasia 0002357
EEG abnormality 0002353
Elevated serum creatine kinase
Elevated blood creatine phosphokinase
Elevated circulating creatine phosphokinase
Elevated creatine kinase
Elevated serum CPK
Elevated serum creatine phosphokinase
High serum creatine kinase
Increased CPK
Increased creatine kinase
Increased creatine phosphokinase
Increased serum CK
Increased serum creatine kinase
Increased serum creatine phosphokinase
[ more ] 		0003236
EMG abnormality 0003457
Emphysema 0002097
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait
[ more ] 		0001288
Generalized muscle weakness 0003324
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
0001639
Seizure 0001250
Type II diabetes mellitus
Noninsulin-dependent diabetes
Type 2 diabetes
Type II diabetes
[ more ] 		0005978
30%-79% of people have these symptoms
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat
[ more ] 		0011675
Atrioventricular block
Interruption of electrical communication between upper and lower chambers of heart
0001678
Dyspnea
Trouble breathing
0002094
Muscular hypotonia
Low or weak muscle tone
0001252
Respiratory insufficiency due to muscle weakness
Decreased lung function due to weak breathing muscles
0002747
5%-29% of people have these symptoms
Hepatomegaly
Enlarged liver
0002240
Macroglossia
Abnormally large tongue
Increased size of tongue
Large tongue
[ more ] 		0000158
Myopathy
Muscle tissue disease
0003198
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections
[ more ] 		0002205
Percent of people who have these symptoms is not available through HPO
Abnormal CNS myelination 0011400
Areflexia
Absent tendon reflexes
0001284
Autosomal recessive inheritance 0000007
Diaphragmatic paralysis
Paralyzed diaphragm
0006597
Dilatation of the cerebral artery 0004944
Fever 0001945
Firm muscles 0003725
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Hearing impairment
Deafness
Hearing defect
[ more ] 		0000365
Proximal muscle weakness
Weakness in muscles of upper arms and upper legs
0003701
Respiratory insufficiency
Respiratory impairment
0002093
Shortened PR interval 0005165
Splenomegaly
Increased spleen size
0001744
Wolff-Parkinson-White syndrome 0001716
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Last updated: 7/1/2020
Mutations in the GAA gene cause glycogen storage disease type 2. The GAA gene provides instructions for producing an enzyme called acid alpha-glucosidase (commonly called acid maltase). This enzyme is active in lysosomes, which are structures that serve as the cell's recycling center. The enzyme normally breaks down glycogen into a simpler sugar called glucose, which is the main energy source for most cells. Mutations in the GAA gene prevent acid alpha-glucosidase from breaking down glycogen, allowing it to build up in the body's cells. Over time, this buildup damages cells throughout the body, particularly muscle cells.[2]
Last updated: 5/14/2015
Glycogen storage disease type 2 is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.[2]
Last updated: 5/14/2015

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.

Newborn Screening

  • An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
  • An Algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a positive newborn screening result. Algorithms are developed by experts in collaboration with the American College of Medical Genetics.
  • Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.
Individuals with glycogen storage disease type 2 are best treated by a team of specialists (such as cardiologist, neurologist, and respiratory therapist) knowledgeable about the disease, who can offer supportive and symptomatic care.  The discovery of the GAA gene has led to rapid progress in understanding the biological mechanisms and properties of the GAA enzyme.  As a result, an enzyme replacement therapy has been developed that has shown, in clinical trials with infantile-onset patients, to decrease heart size, maintain normal heart function, improve muscle function, tone, and strength, and reduce glycogen accumulation.  A drug called alglucosidase alfa (Myozyme©) has received FDA approval for the treatment of glycogen storage disease type 2. Myozyme is a form of GAA—the enzyme that is absent or reduced in this condition. The drug is usually administered via intravenous infusion every other week. Myozyme has been remarkably successful in reversing cardiac muscle damage and in improving life expectancy in those with the infantile form of the disease. [1][3] To find out more information on Myozyme, please visit the following link: http://www.myozyme.com/. Another alglucosidase alfa drug called Lumizyme has also been approved for the treatment of this condition.[5] More information about Lumizyme can be accessed through the following link: http://www.lumizyme.com/patients.aspx.
Last updated: 5/14/2015

Management Guidelines

  • The American College of Medical Genetics (ACMG) provides education, resources, and a voice for the medical genetics profession.  To make genetic services available to and improve the health of the public, the ACMG promotes the development and implementation of methods to diagnose, treat and prevent genetic diseases. In an effort to fulfill its mission, the ACMG performs many tasks, including developing clinical practice guidelines.  In May 2006, the ACMG Work Group on Management of Pompe Disease released a ACMG Practice Guideline titled "Pompe disease diagnosis and management guideline." To view this practice guideline, visit the link above.
  • The NORD Physician Guide for Glycogen storage disease type 2 was developed as a free service of the National Organization for Rare Disorders (NORD) and it's medical advisors.  The guides provide a resource for clinicians about specific rare disorders to facilitate diagnosis and treatment of their patients with this condition. 

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

  • Recombinant human acid alpha-glucosidase; alglucosidase alfa (Brand name: Lumizyme) - Manufactured by Genzyme Corporation
    FDA-approved indication: Lumizyme for patients 8 years and older with late (non-infantile) onset Pompe disease (GAA deficiency) who do not have evidence of cardiac hypertrophy. The safety and efficacy of Lumizyme (alglucosidase alfa) have not been evaluated in controlled clinical trials in infantile-onset patients, or in late (non-infantile) onset patients less than 8 years of age.
    National Library of Medicine Drug Information Portal
  • Recombinant human acid alpha-glucosidase (Brand name: Myozyme®) - Manufactured by Genzyme Corporation
    FDA-approved indication: For use in patients with Pompe disease (GAA deficiency). Alglucosidase alfa has been shown to improve ventilator-free survival in patients with infantile onset Pompe disease as compared to an untreated historical control, whereas use of Alphaglucosidase in patients with other forms of Pompe disease has not been adequately studied to assure safety and efficacy.
    National Library of Medicine Drug Information Portal

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

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 2. 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.

Patient Registry

  • The Pompe Registry supports research for Glycogen storage disease type 2 by collecting information about patients with this diagnosis. You can join the registry to share your information with researchers and receive updates about participating in new research studies. Learn more about registries.

  • The Lysosomal Disease Network is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with this condition through research. The Lysosomal Disease Network has a registry for patients who wish to be contacted about clinical research opportunities.

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

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

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

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 2. Click on the link to view a sample search on this topic.

Press Releases

  • The U.S. Food and Drug Administration (FDA) provides information about an FDA-approved treatment for Pompe disease called Myozyme through a 2006 Press Release. To view this information, click on the above link.

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

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  1. Plotz P. Pompe Disease. National Organization for Rare Disorders (NORD). 2017; http://rarediseases.org/rare-diseases/pompe-disease/.
  2. Pompe disease. Genetics Home Reference (GHR). February 2016; http://ghr.nlm.nih.gov/condition/pompe-disease.
  3. NINDS Pompe Disease Information Page. National Institute of Neurological Disorders and Stroke (NINDS). 2017; https://www.ninds.nih.gov/Disorders/All-Disorders/Pompe-Disease-Information-Page.
  4. Leslie N & Tinkle BT. Glycogen Storage Disease Type II (Pompe Disease). GeneReveiws. 2017; http://www.ncbi.nlm.nih.gov/books/NBK1261.
  5. FDA expands approval of drug to treat Pompe disease to patients of all ages; removes risk mitigation strategy requirements. U.S. Food and Drug Administration (FDA). https://www.accessdata.fda.gov/drugsatfda_docs/bla/2014/125291orig1s136.pdf.