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Disease Profile

Glycogen storage disease type 2

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Antenatal

ICD-10

E74.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Pompe disease; Acid maltase deficiency disease; Aglucosidase alfa;

Categories

Heart Diseases; Nervous System Diseases; RDCRN

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]

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]

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.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Oligosacchariduria
0010471
Progressive proximal muscle weakness
0009073
30%-79% of people have these symptoms
Areflexia
Absent tendon reflexes
0001284
Cardiomegaly
Enlarged heart
Increased heart size

[ more ]

0001640
Difficulty climbing stairs
Difficulty walking up stairs
0003551
Difficulty walking
Difficulty in walking
0002355
Elevated serum alanine aminotransferase
0031964
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: myopathic abnormalities
0003458
Exercise intolerance
Decreased ability to exercise
Inability to exercise

[ more ]

0003546
Exertional dyspnea
0002875
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Fatigue
Tired
Tiredness

[ more ]

0012378
Feeding difficulties in infancy
0008872
Glycogen accumulation in muscle fiber lysosomes
0030231
Gowers sign
0003391
Heart murmur
Heart murmurs
0030148
Hepatomegaly
Enlarged liver
0002240
Hyporeflexia
Decreased reflex response
Decreased reflexes

[ more ]

0001265
Increased lactate dehydrogenase level
0025435
Left ventricular hypertrophy
0001712
Lower limb muscle weakness
Lower extremity weakness
Lower limb weakness
Muscle weakness in lower limbs

[ more ]

0007340
Motor delay
0001270
Respiratory insufficiency due to muscle weakness
Decreased lung function due to weak breathing muscles
0002747
Respiratory tract infection
Respiratory infection
0011947
5%-29% of people have these symptoms
Abnormal internal carotid artery morphology
3000062
Basilar artery calcification
0031310
Chronic pain
Long-lasting pain
0012532
Cranial nerve paralysis
0006824
Diaphragmatic weakness
Weak diaphragm
0009113
Difficulty in tongue movements
0000183
Dilatation of the cerebral artery
0004944
Dysarthria
Difficulty articulating speech
0001260
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Facial hypotonia
Decreased facial muscle tone
Low facial muscle tone
Reduced facial muscle tone

[ more ]

0000297
Fatigable weakness of respiratory muscles
0030196
Fatigable weakness of swallowing muscles
0030195
Generalized muscle weakness
0003324
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hyperlordosis
Prominent swayback
0003307
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
0001639
Impaired mastication
Chewing difficulties
Chewing difficulty
Difficulty chewing

[ more ]

0005216
Inability to walk
0002540
Infantile muscular hypotonia
Decreased muscle tone in infant
0008947
Left ventricular outflow tract obstruction
0032092
Macroglossia
Abnormally large tongue
Increased size of tongue
Large tongue

[ more ]

0000158
Orthopnea
0012764
Osteoporosis
0000939
Ptosis
Drooping upper eyelid
0000508
Respiratory distress
Breathing difficulties
Difficulty breathing

[ more ]

0002098
Respiratory failure
0002878
Scoliosis
0002650
Shortened PR interval
0005165
Sleep apnea
Pauses in breathing while sleeping
0010535
Thoracic aortic aneurysm
0012727
Transient ischemic attack
Mini stroke
0002326
Vasculitis
Inflammation of blood vessel
0002633
1%-4% of people have these symptoms
Atelectasis

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]

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.

    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.

      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: https://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: https://www.lumizyme.com/patients.aspx.

      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

        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

          Organizations Providing General Support

            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

              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.

                  References

                  1. Plotz P. Pompe Disease. National Organization for Rare Disorders (NORD). 2017; https://rarediseases.org/rare-diseases/pompe-disease/.
                  2. Pompe disease. Genetics Home Reference (GHR). February 2016; https://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; https://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.

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