Glycogen storage disease type 2

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 caused by an inborn lack of the enzyme acid alpha-glucosidase (also known as acid maltase), which is necessary to break down glycogen, a substance that is a source of energy for the body. This enzyme deficiency causes excess amounts of glycogen to accumulate in the lysosomes, which are structures within cells that break down waste products within the cell. This accumulation of glycogen in certain tissues, especially muscles, impairs their ability to function normally.^[1]^[2] Glycogen storage disease type 2 is a single disease continuum with variable rates of disease progression.^[1] 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.^[1]^[3] Another similar drug called Lumizyme has recently been approved for the treatment this disease.^[3]^[4]

Last updated: 5/14/2015

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]^[5]

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

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Aplasia/Hypoplasia of the abdominal wall musculature	90%
Cardiomegaly	90%
Cognitive impairment	90%
EEG abnormality	90%
EMG abnormality	90%
Emphysema	90%
Feeding difficulties in infancy	90%
Gait disturbance	90%
Hypertrophic cardiomyopathy	90%
Neurological speech impairment	90%
Seizures	90%
Type II diabetes mellitus	90%
Arrhythmia	50%
Muscular hypotonia	50%
Abnormality of the tongue	7.5%
Hepatomegaly	7.5%
Myopathy	7.5%
Recurrent respiratory infections	7.5%
Abnormal CNS myelination	-
Areflexia	-
Autosomal recessive inheritance	-
Cerebral aneurysm	-
Diaphragmatic paralysis	-
Dyspnea	-
Elevated serum creatine phosphokinase	-
Fever	-
Firm muscles	-
Hearing impairment	-
Macroglossia	-
Proximal muscle weakness	-
Respiratory insufficiency due to muscle weakness	-
Shortened PR interval	-
Splenomegaly	-
Wolff-Parkinson-White syndrome	-

Last updated: 9/1/2016

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.^[4] 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.
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.
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

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 studying or have studied Glycogen storage disease type 2. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

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

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD. Suggest an organization to add.

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, Hampshire, 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/
Children Living with Inherited Metabolic Diseases (CLIMB)
Climb Building
176 Nantwich Road
Crewe CW2 6BG
United Kingdom
Toll-free: 0800 652 3181
Telephone: 0845 241 2173
E-mail: contact@climb.org.uk
Website: http://www.climb.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/
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

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.

Genetics 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 GeneTests, 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.

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

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

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
WORLD Symposium 2010 (Lysosomal Disease Network's 6th Annual Research Meeting) Wednesday, February 10, 2010 - Friday, February 12, 2010
Location: Miami Hilton Downtown, Miami, Florida
Description: The specific aims of this meeting were to (1) emphasize the strategies for, and identify the obstacles to, moving from translational research to clinical trials; (2) coalesce members of the LD network into functional research collaborations and present to the LDN community progress on the specific projects that are part of the funded U54 RDCRN grant; (3) foster interdisciplinary collaboration with the overall goal of improving knowledge of basic discoveries and clinical manifestations of these diseases; (4) provide an educational forum for young investigators, clinicians, and researchers in the field; (5) identify and discuss the latest findings in the natural history of lysosomal diseases, diagnostic testing and screening, and treatment, with specific focus on (a) inflammatory components of lysosomal diseases and autophagy, especially in the central nervous system, (b) new treatments of the central nervous systems, and (c) ethics and efficacy in treating the presymptomatic or asymptomatic patient; and (6) identify areas requiring additional basic and clinical research and public policy and regulatory attention, such as ethics and economics, and factors that impact implementation of therapy, including newborn screening.

Contact: Dr. Danilo A. Tagle(301) 496-5745tagled@mninds.nih.gov

Co-funding Institute(s): National Institute of Neurological Disorders and Stroke, Office of Rare Diseases Research
- Agenda ( - 2715KB)

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References References

Plotz P. Pompe Disease. National Organization for Rare Disorders (NORD). 2013; 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). February 20, 2013; http://www.ninds.nih.gov/disorders/pompe/pompe.htm. Accessed 5/14/2015.
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). August 1, 2014; http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm407563.htm. Accessed 5/14/2015.
Nancy Leslie, MD and Brad T Tinkle, MD, PhD. Glycogen Storage Disease Type II (Pompe Disease). GeneReveiws. May 9, 2013; http://www.ncbi.nlm.nih.gov/books/NBK1261. Accessed 6/20/2016.