Pompe Disease

National Organization for Rare Disorders, Inc.

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It is possible that the main title of the report Pompe Disease is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.


  • acid maltase deficiency (AMD)
  • acid alpha glucosidase (GAA) deficiency
  • glycogen storage disease type II

Disorder Subdivisions

  • None

General Discussion


Pompe disease is a rare multisystem genetic disorder that is characterized by absence or deficiency of the lysosomal enzyme alpha-glucosidase (GAA). This enzyme is required to breakdown (metabolize) the complex carbohydrate glycogen and convert it into the simple sugar glucose. Glycogen is a thick, sticky substance and failure to properly break it down results in massive accumulation of lysosomal glycogen in cells, particularly in cardiac, smooth, and skeletal muscle cells. Pompe disease is a single disease continuum with variable rates of disease progression and different ages of onset. The infantile form is characterized by severe muscle weakness 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). Without treatment, progressive cardiac failure usually causes life-threatening complications by the age of 12 to 18 months. Pompe disease can also present in childhood, adolescence or adulthood, collectively known as late-onset Pompe disease. The extent of organ involvement may vary among affected individuals; however, skeletal muscle weakness is usually present with minimal cardiac involvement. Initial symptoms of late-onset Pompe disease may be subtle and may go unrecognized for years. Pompe disease is caused by mutations of the GAA gene and is inherited as an autosomal recessive trait.


Pompe disease belongs to a group of diseases known as the lysosomal storage disorders. Lysosomes are particles bound in membranes within cells that function as the primary digestive units of cells. Enzymes within the lysosomes break down or digest particular nutrients, such as complex molecules composed of a sugar attached to a protein (glycoproteins). There are more than 40 different lysosomal enzymes. Low levels or inactivity of the GAA lysosomal enzyme leads to the accumulation of glycogen in the lysosomes of various cells within the body with unwanted consequences. Pompe disease may also be classified as a glycogen storage disease, a group of metabolic disorders characterized by abnormalities involving the use and/or storage of glycogen.


Pompe disease is a disease continuum. Generally, the disorder is broken down into an infantile form and a late (or delayed) onset form.

Infantile Form

Individuals with the infantile form are the most severely affected. Although these infants usually appear normal at birth, the disease presents within the first two or three months of life with rapidly progressive muscle weakness, diminished muscle tone (hypotonia), and a type of heart disease known as hypertrophic cardiomyopathy, a condition characterized by abnormal thickening of the walls of the heart resulting in obstruction of blood flow in and out of the heart. In most cases, the left ventricle is affected. Symptoms of hypertrophic cardiomyopathy vary widely among affected individuals. Affected infants and children may experience shortness of breath upon exertion, fatigue, excessive sweating, and poor appetite and weight gain resulting in growth failure. As affected children age, they may experience chest pain or discomfort, irregular heartbeats, dizziness or fainting episodes (syncope) usually upon heavy exertion, and, eventually, congestive heart failure and fluid accumulation within the lungs. In some cases, affected individuals may experience sudden cardiac arrest and, potentially, sudden death.

Many infants have a large, protruding tongue and a moderate enlargement of the liver. Infants may appear floppy and may be unable to move their arms and legs properly. The legs often rest in a frog position and feel firm on palpation (pseudo-hypertrophy).

Feeding and swallowing problems as well as respiratory difficulties, which are often combined with respiratory tract infections, are common. Major developmental milestones such as rolling over, sitting up, and standing are delayed or not achieved. Mental development is usually normal. Some infants may experience hearing loss. The infantile form of Pompe disease is characterized by a total lack of alpha glucosidase activity and by a rapid buildup of glycogen in skeletal muscle and in the heart.

Late Onset Forms

The time of presentation of late onset Pompe disease varies from the first to the seventh decade. Patients who develop symptoms early in life tend to be the more severely affected. Late onset patients have varying amounts of residual acid alpha-glucosidase activity. Glycogen buildup is not as rapid as in the infantile form, but the disease is progressive and can greatly affect the quality of life and decrease the lifespan of an affected person.

Late onset Pompe disease is generally associated with progressive proximal muscle weakness, varying degrees of respiratory weakness and little to no cardiac involvement. The lower limbs are affected more often than the upper limbs. The muscles adjacent to the spinal column (paraspinal muscles) and neck muscles are often involved. Overall, the extent of organ involvement is highly variable. The disease progresses more slowly than the infantile form. However, progressive muscle weakness can eventually cause serious complications including swallowing difficulties, difficulty walking and severe respiratory failure. Respiratory tract infections may be frequent. Affected individuals may require a wheelchair or become ventilator dependent. Late onset Pompe disease can shorten life expectancy.

When late onset Pompe disease develops during childhood, symptoms may include delays in achieving motor milestones. In some cases, this may resemble other neuromuscular disorders such as muscular dystrophy. Children with late onset Pompe disease may also develop drooping of the upper eyelids (ptosis), abnormal enlargement of the liver, abnormal curvature of the spine (scoliosis), and tightening of certain joints resulting in restricted or stiff movements (contractures). Affected individuals may also experience difficulty chewing and/or swallowing.

When late onset Pompe disease occurs during adulthood, the pattern of muscle weakness exhibited is similar to that found in other chronic muscle disorders and tends to affect lower limbs more than upper limbs. Approximately one-third of the adult cases present with respiratory failure, and initial symptoms may include headache at night or upon awakening, sleeping difficulties including sleep apnea, nausea, fatigue, difficulty breathing except in an upright position (orthopnea), and labored breathing upon exertion (exertional dyspnea).


Pompe disease is caused by mutation of the acid alpha-glucosidase gene (GAA) gene. More than 100 different mutations in the GAA gene have been identified in families with this disorder. Mutations of the GAA gene in Pompe disease are inherited as an autosomal recessive trait.

Genetic diseases are determined by two genes, one received from the father and one from the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.

The GAA gene has mapped to the long arm (q) of chromosome 17(17q25.2-q25.3). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 17q25.2-q25.2" refers to bands 25.2-25.3 on the long arm of chromosome 17. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

The symptoms of Pompe disease are caused by a complete or partial deficiency of the enzyme acid alpha-glucosidase that normally breaks down lysosomal glycogen into glucose. In infantile Pompe disease there is less than 1% of GAA enzyme activity; in late onset Pompe disease residual GAA enzyme activity can range from 2%-40%. Glycogen, therefore, accumulates within the lysosomes of several tissues (mainly the muscles), interferes with cellular function, and causes cell damage and ultimately the various symptoms of the disorder. In the late onset form, effects typically are seen in the skeletal and respiratory muscles of the patient. In the infantile form, glycogen also accumulates in the heart.

Affected Populations

Pompe disease occurs in various populations and ethnic groups around the world. Estimates of vary, but its incidence is generally placed at approximately 1 in 40,000 births in the United States. Many late onset cases go misdiagnosed or undiagnosed, making it difficult to determine the true frequency of Pompe disease in the general population. Males and females are affected in equal numbers and the disorder has been reported in individuals of every race and ethnic group around the world.

Standard Therapies


A diagnosis of Pompe disease is based upon a thorough clinical evaluation, a detailed patient and family history, and a variety of tests. Prenatal diagnosis is possible when a pregnancy is believed to be at risk for Pompe disease.

Clinical Testing and Work Up

In individuals suspected of having Pompe disease, a blood sample (dried blood spots) can be taken and an enzyme assay, a test that measures the activity of a specific enzyme, can be performed. An enzyme assay can also be performed on drawn blood, in which the enzyme activity of GAA is measured in certain white blood cells called lymphocytes. These exams are a reliable and convenient means of diagnosing Pompe disease.

When a diagnosis of Pompe disease is based upon a blood-based enzyme assay, it must be confirmed through molecular genetic testing or by another assay on a separate blood or tissue sample. Molecular genetic testing can detect mutations in the GAA gene that causes Pompe disease.

In the past, surgical removal and microscopic study (biopsy) of samples of skin and muscle tissue was used to help diagnosis Pompe disease. However, these exams can take weeks to process, thereby causing a delay in the initiation of treatment. Skin and muscle biopsies are no longer necessary to obtain a diagnosis of Pompe disease.

A variety of additional tests may be performed to detect or assess symptoms potentially associated with Pompe disease such as sleep studies, breathing tests to measure lung capacity, and electromyography, a test to measure muscle function. During an electromyography, a needle with an attached electrode is inserted through the skin and into the muscle. The electrode detects and records the electrical activity of the muscle at rest and when it contracts. This information can determine whether damage to muscle or nerves is present.

Specific tests may also performed to assess the heart including chest x-rays, electrocardiogram, and echocardiogram. Chest x-rays allows physicians to assess the size of the heart, which can be enlarged in some infants with Pompe disease. An electrocardiogram measures the electrical activity of the heart and can detect abnormal heart rhythms. An echocardiogram uses reflected sound waves to create a picture of the heart and can reveal abnormal thickening of the heart muscle tissue.

In families with a known mutation of the GAA gene, prenatal diagnosis is possible through chorionic villi sampling (CVS) or amniocentesis. During CVS, fetal tissue samples are removed and enzyme tests (assays) are performed on cultured tissue cells (fibroblasts) and/or white blood cells (leukocytes). During amniocentesis, a sample of the fluid that surrounds the developing fetus is removed and studied.

In cases where a parent has a known genetic abnormality (i.e. carrier), pre-implantation genetic diagnosis (PGD) may be an option. PGD can be performed on embryos created through in vitro fertilization. PGD refers to testing an embryo to determine whether it has the same genetic abnormality as the parent. Families interested in such an option should seek the counsel of a certified genetics professional.


The treatment of Pompe disease is both disease-specific and symptomatic and supportive. Treatment may require the coordinated efforts of a team of specialists with expertise in treating neuromuscular disorders. Pediatricians or internists, neurologists, orthopedists, cardiologists, dieticians, and other healthcare professionals may need to systematically and comprehensively plan an affect child's treatment. Genetic counseling will be of benefit for affected individuals and their families.

In April of 2006, the U.S. Food and Drug Administration (FDA) approved the enzyme replacement therapy Myozyme® for patients with infantile onset Pompe disease. Lumizyme® was approved by the FDA in 2010. Myozyme is used for patients younger than 8 years old; Lumizyme is used for patients older than 8 years old. All patients enzyme replacement therapy is recommended every two weeks via intravenous administration of genetically engineered (recombinant) human acid alpha-glucosidase at a dose of 20 mg/kg body weight. Myozyme and Lumizyme are manufactured by the Genzyme Corporation. For information, go to www.genzyme.com or contact the company at:

Genzyme Corporation

500 Kendall Street

Cambridge, MA 02142

Tel.: (617) 252-7500

Fax: (617) 252-7600

Additional treatment of Pompe disease is symptomatic and supportive. Respiratory support may be required, as most patients have some degree of respiratory compromise and/or respiratory failure. Physical therapy may help to strengthen respiratory muscles. Some patients may need respiratory assistance during the night or periods of the day or during respiratory tract infections may be helpful. Some patients may require mechanical ventilation support, which can include noninvasive and invasive techniques. The decision about the duration of respiratory support is best made by the family in careful consultation with the patient's physicians and other members of the healthcare team based upon the specifics of the case.

Physiotherapy is recommended to improve strength and physical ability. Occupational therapy, including the use of canes or walkers, may be necessary. Eventually, some individuals may require the use of a wheelchair. Speech therapy can be beneficial to improve articulation and speech in some cases.

Orthopedic devices including braces may be recommended in some cases. Surgery may be required for certain orthopedic symptoms such as contractures or spinal deformity.

Since Pompe disease can weaken muscles used for chewing and swallowing, adequate measures may be required to ensure proper nutrition and weight gain. Some patients may need specialized, high-calorie diets and learn techniques to change the size and texture of food to lower the risk of aspiration. Some infants may require the insertion of a feeding tube that is run through the nose, down the esophagus and into the stomach (nasogastric tube). In rare cases, a feeding tube may need to be inserted directly into the stomach through a small surgical opening in the abdominal wall. Some individuals with late onset Pompe disease may require a soft diet, but few require feeding tubes.

Investigational Therapies

Gene therapy is also being studied as another approach to therapy for individuals with Pompe disease. In gene therapy, the defective gene present in a patient is replaced with a normal gene to enable the produce of the active enzyme and prevent the development and progression of the disease in question. Given the permanent transfer of the normal gene, which is able to produce active enzyme at all sites of disease, this form of therapy is theoretically most likely to lead to a "cure." However, at this time, there remain some technical difficulties to resolve before gene therapy can be advocated as a viable alternative approach for Pompe disease.

Researchers are also studying modifications to existing enzyme replacement therapy in an effort to improve effectiveness. This includes exploring ways to improve the uptake of recombinant acid alpha-glucosidase by muscle cells.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Toll-free: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:


For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/



Cupler EJ, Berger KI, Leshner RT, et al. Consensus treatment recommendations for late-onset Pompe disease. Muscle Nerve. 2012;45:319-333. http://www.ncbi.nlm.nih.gov/pubmed/22173792

Gungor D, de Vries JM, Hop WC, et al. Survival and associated factors in 268 adults with Pompe disease prior to treatment with enzyme replacement therapy. Orphanet J Rare Dis. 2011;6:34. http://www.ncbi.nlm.nih.gov/pubmed/21631931

Van Capelle CI, Goedegebure A, Homans NC, et al. Hearing loss in Pompe disease revisited: results from a study of 24 children. J Inherit Metab Dis. 2010;33:597-602. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946566/

Winchester B, Bali D, Bodamer OA, et al. Methods for a prompt and reliable laboratory diagnosis of Pompe disease: report from an international consensus meeting. Mol Genet Metab. 2008;93:275-281. http://www.ncbi.nlm.nih.gov/pubmed/18078773

Kishnani PS, Steiner RD, Bali D, et al. Pompe disease diagnosis and management guideline. Genet Med. 2006;8:267-288. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110959/

Anneser JMH, Pongratz DE, Podskarbi T, Shin YS, Schoser BGH. Mutations in the acid alpha-glucosidase gene (M. Pompe) in a patient with an unusual phenotype. Neurology. 2005;64:368-70. http://www.ncbi.nlm.nih.gov/pubmed/15668445

Hagemans MLC, Winkel LPF, Hop WCJ, et al. Disease severity in children and adults with Pompe disease related to age and disease duration. Neurology. 2005;64:2139-41.


Amalfitano A, Bengur AR, Morse RP, et al. Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I/II clinical trial. Genet Med. 2001;3:132-38. http://www.ncbi.nlm.nih.gov/pubmed/11286229

van den Haut JM, Reuser AJ, de Klerk JB, et al. Enzyme therapy for Pompe disease with recombinant human alpha-glucosidase from rabbit milk. J Inherit Metab Dis. 2001;24:266-74.


Ausems MG, ten Berg K, Sandkuijl LA, et al. Dutch patients with glycogen storage disease type II show common ancestry for the 525delT and del exon 18 mutations. J Med Genet. 2001;38:527-29. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1734921/

Umapathysivam K, Hopwood JJ, Meikle PJ. Determination of acid alpha-glucosidase activity in blood spots as a diagnostic test for Pompe disease. Clin Chem. 2001;47:1378-83.


Martiniuk F, Chen A, Donnabella V, et al. Correction of glycogen storage disease type II by enzyme replacement with a recombinant human acid maltase produced by over-expression in a CHO-DHFR(neg) cell line. Biochem Biophys Res Comm. 2000;276:917-23.


Chen YT, Amalfitano A. Towards a molecular therapy for glycogen storage disease type II (Pompe Disease). Mol Med Today. 2000;6:245-51.


Ausems MG, ten Berg K, Beemer FA, et al. Phenotypic expression of late-onset glycogen storage disease Type II: identification of asymptomatic adults through family studies and review of reported families. Neuromuscul Disord. 2000;10:467-71.



Tinkle BT, Leslie N. Updated:08/12/2010. Glycogen Storage Disease Type II (Pompe Disease). In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2003. Available at http://www.ncbi.nlm.nih.gov/books/NBK1509/ Accessed: March 10, 2013.

Froissart R, Maire I. Glycogen storage disease due to acid maltase deficiency. Orphanet Encyclopedia, July 2007. Available at: http://www.orpha.net/ Accessed: March 10, 2013.


CLIMB (Children Living with Inherited Metabolic Diseases)

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Association for Glycogen Storage Disease

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Acid Maltase Deficiency Association, Inc.

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Association for Glycogen Storage Disease (UK) Ltd

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For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.