Glycogen storage disease type 2

Información en español Title

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

Categories:

Heart Diseases; Nervous System Diseases; RDCRN

Summary Summary

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

Symptoms Symptoms

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	Learn More: 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 phosphokinase	Elevated blood creatine phosphokinase Elevated circulating creatine phosphokinase Elevated creatine kinase Elevated serum CPK Elevated serum creatine kinase 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
Seizures	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		0001678
Dyspnea	Trouble breathing	0002094
Muscular hypotonia	Low or weak muscle tone	0001252
Respiratory insufficiency due to muscle weakness		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		0003701
Respiratory insufficiency	Respiratory impairment	0002093
Shortened PR interval		0005165
Splenomegaly	Increased spleen size	0001744
Wolff-Parkinson-White syndrome		0001716

Showing of 37 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 8/7/2018

Do you have updated information on this disease? We want to hear from you.

Cause Cause

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

Inheritance Inheritance

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

Diagnosis Diagnosis

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.

Treatment Treatment

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

Find a Specialist Find a Specialist

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

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Research Research

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

Pompe Registry
Genzyme Corporation
500 Kendall Street
Cambridge, MA 02142
Toll-free: 1-800-745-4447, X. 15500
Telephone: 617-591-5500
Fax: 617-374-7339
Email: https://www.lsdregistry.net/pomperegistry/hcp/contact/preg_hc_contact.asp
Web site: https://www.lsdregistry.net/pomperegistry/
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.

Organizations Organizations

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

Acid Maltase Deficiency Association (AMDA)
P.O. Box 700248
San Antonio, TX 78270
Telephone: 210-494-6144
Fax: 210-490-7161
E-mail: tianrama@aol.com
Website: http://www.amda-pompe.org
Association for Glycogen Storage Disease
PO Box 896
Durant, IA 52747
Telephone: 1-563-514-4022
E-mail: info@agsdus.org
Website: http://www.agsdus.org
Association for Glycogen Storage Disease UK
Old Hambledon Racecourse
Sheardley Lane
Droxford, Southampton, SO32 3QY
United Kingdom
Telephone: 0300 123 2790 (Office hrs, Mon-Thurs) or 0300 123 2799 (Out of hours)
Website: http://www.agsd.org.uk/
International Pompe Association
Paula Waddell, c/o VSN
Luitenant Generaal van Heutszlaan 6
3743 JN Baarn
Netherlands
Telephone: +31(35)5480480
Fax: +31(35)5480499
E-mail: info@worldpompe.org
Website: http://www.worldpompe.org/
Metabolic Support UK
5 Hilliards Court
Sandpiper Way
Chester Business Park
Chester, CH4 9QP United Kingdom
Toll-free: 0800 652 3181
Telephone: 0845 241 2173
E-mail: https://www.metabolicsupportuk.org/contact-us
Website: https://www.metabolicsupportuk.org
Muscular Dystrophy Association (MDA)
222 S Riverside Plaza
Suite 1500
Chicago, IL 60606
Toll-free: 800-572-1717
TTY: 1-800-572-1717
E-mail: mda@mdausa.org
Website: http://www.mdausa.org/
United Pompe Foundation
c/o David W. Hamlin
5100 N. Sixth Street #119
Fresno, CA 93710
Telephone: (559) 227-1898
Fax: (559) 227-1898
E-mail: david@unitedpompe.com
Website: http://www.unitedpompe.com/index.cfm

Do you know of an organization? We want to hear from you.

Living With Living With

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

The Social Security Administration has included this condition in their Compassionate Allowances Initiative. This initiative speeds up the processing of disability claims for applicants with certain medical conditions that cause severe disability. More information about Compassionate Allowances and applying for Social Security disability is available online.

Learn More 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

The American Society of Gene & Cell Therapy provides information on the treatment of lysosomal storage diseases.
Genetics Home Reference (GHR) contains information on Glycogen storage disease type 2. This website is maintained by the National Library of Medicine.
The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
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 2. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

Talsma, et al., A Rare Presentation of Childhood Pompe Disease: Cardiac Involvement Provoked by Epstein-Barr Virus Infection. Pediatrics 2002;109:e65.
Van den Hout, et al., Long-Term Intravenous Treatment of Pompe Disease With Recombinant Human {alpha}-Glucosidase From Milk, Pediatrics 2004;113: e448-e457.

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.

News & Events News & Events

NCATS Co-Sponsored Conferences

Newborn Screening for Neuromuscular Diseases: Improving Patient Outcomes and Evaluating Public Health Impact Thursday, March 3, 2016 - Saturday, March 5, 2016
Location: St. Louis, MO
Description: This two-day international meeting will bring together experts in newborn screening, pediatrics, and neuromuscular disease as well as other public health stakeholders to review key topics in newborn screening for Pompe disease (already included in the Recommended Universal Screening Panel) and Duchenne muscular dystrophy (DMD) where pilot screening has already begun in the US. The primary goal of this meeting will be addressing the components of 1) laboratory screening and 2) short- and long-term clinical follow-up needed to ensure improved health outcomes in Pompe disease and DMD. We will also discuss how these programs can be implemented to efficiently collect information about the public health and societal impact of population-based neuromuscular screening programs.

Contact: Yaffa Rubinstein, Ph.D.(301) 402-4338yaffa.rubinstein@nih.gov

Co-funding Institute(s): National Institute of Child Health and Human Development, Office of Rare Diseases Research
Gordon Research Conference and Gordon Research Seminar on Lysosomes and Endocytosis Sunday, June 15, 2014 - Friday, June 20, 2014
Location: Proctor Academy, Andover, NH
Description: The main goal of the Lysosomes and Endocytosis GRC is to foster the dissemination of current research results and the establishment of new research areas and new collaborations in the area of the cell biology of endocytosis, lysosomes, endosomes and related organelles. We hope that many of these new directions and collaborations will be directed toward the etiology, diagnosis and treatment of rare genetic diseases such as lysosomal storage disorders, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Niemann Pick disease and tuberous sclerosis, among others.

Contact: Alexandra Ainsztein, Ph.D.(301) 594-0828, Alexandra.Ainsztein@nih.gov

Co-funding Institute(s): National Institute of General Medical Sciences, Office of Rare Diseases Research

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References References

Plotz P. Pompe Disease. National Organization for Rare Disorders (NORD). 2017; http://rarediseases.org/rare-diseases/pompe-disease/.
Pompe disease. Genetics Home Reference (GHR). February 2016; http://ghr.nlm.nih.gov/condition/pompe-disease.
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.
Leslie N & Tinkle BT. Glycogen Storage Disease Type II (Pompe Disease). GeneReveiws. 2017; http://www.ncbi.nlm.nih.gov/books/NBK1261.
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.