What Is Pompe Disease?

  • 1st Revision: Beatriz Roque
  • 2nd Revision: Tan Jit Yih

Pompe disease is a rare genetic disorder that prevents the breakdown of glycogen, impairing the functioning of the heart and skeletal muscles.2 This metabolic disorder affects 1 in 40,000 individuals from birth through to adulthood.3 

In this article, we will explore the following key topics of Pompe disease:

  • Types of Pompe disease
  • Signs and Symptoms of Pompe disease
  • Management and Treatment of Pompe disease


Pompe disease (GSDII) is a genetically inherited condition caused by a mutation of a gene that is responsible for the production of lysosomal acid-alpha-glucosidase (GAA). GAA is an enzyme responsible for the breakdown of glycogen, a form of glucose that is used as an energy supply to organs. 

In the absence of GAA, the breakdown of glycogen does not occur, which leads to an accumulation of glycogen in the liver and muscles. In turn, this leads to the deterioration of all muscle types - the liver, the nervous system - causing complications such as dysfunctional muscles, respiratory insufficiency, and feeding and urinary difficulties.2

This disease is inherited in an autosomal recessive manner, which means that both parents have to be carriers of the gene for it to be passed down to their children. 

The severity of the disease depends on how much GAA is produced, which varies according to the age of onset and rate of progression of the disease. GSDII can be diagnosed and managed with various treatments, including enzyme replacement therapy, oral chaperone therapy, and modified rhGAA.2

Types of pompe disease 

This disease is marked by a wide variety of characteristics which has created inconsistency in the terminology used for each subtype of Pompe disease. 

The two main categories are infantile and late-onset.

The classic infantile-onset represents the most severe form of the disease andis characterised by muscle weakness, poor muscle tone, enlarged liver (referred to as hepatomegaly) and enlarged heart (cardiomegaly), which can, in turn, lead to heart failure.

The non-classic infantile-onset and late-onset forms of Pompe disease are characterised by less severe forms of heart disease (cardiomyopathy) and muscle disease (myopathy), as well as slower muscle weakness progression.4 Patients with these forms of Pompe disease are also affected by progressive limitation of neck and trunk movements, scoliosis, and can become underweight.2

Causes of pompe disease 

As mentioned above, Pompe disease is caused by a genetic mutation that limits the production of GAA, an enzyme responsible for the breakdown of glycogen. In turn, this leads to the accumulation of glycogen in our cells, impacting a fundamental cellular process called autophagy through which cells degrade cellular components like damaged proteins, organelles, and amyloids.6,9 Autophagy induces the formation of autophagolysosome, a double-membrane autophagosome that degrades these components with lysosomal enzymes.6,9 The progressive storage of glycogen in autophagic vacuoles due to GAA absence causes autophagy disruption that leads to impairment of muscle contractile units.9 

Other associated processes that are also impacted and that contribute to tissue damage include oxidative stress, calcium homeostasis, and mitochondrial abnormalities.9

Signs and symptoms of pompe disease 

The severity of this disease is affected by the level of production of the GAA enzyme that is maintained and thus can manifest in various different symptoms and signs, some of which overlap with other metabolic disorders.5 

Typically, the onset of Pompe disease in newborns leads to symptoms such as:2,4,5 

  • Decreased muscle tone (hypotonia)
  • Limbic weakness
  • Enlargement of the tongue (macroglossia)
  • Thickening of the heart muscle (hypertrophic cardiomyopathy)
  • Enlargement of the liver (hepatomegaly)
  • Cardiorespiratory insufficiency 

Adolescents and adults with Pompe disease typically present with different symptoms:2,4,5

  • Progressive weakening of the upper neck and trunk
  • Rigid spine syndrome
  • Scoliosis
  • Decreased body mass
  • Respiratory deterioration

Among the symptoms experienced by patients with Pompe disease, respiratory failure is the leading cause of mortality and morbidity.2 

Management and treatment for pompe disease 

Pompe disease can be cured with proper treatment, though this varies according to the patient’s needs. 

Enzyme replacement therapy (ERT) with recombinant acid alpha-glucosidase (rhGAA), a precursor of the enzyme GAA, is the standard of care for patients with this disease. This therapy helps to strengthen the cardiac and skeletal muscles and improve respiratory function, which has a significant impact on the lifespan of patients.8 However, it’s been observed that the body may create an immune response against the rhGAA, decreasing the efficacy and survival rate of patients. 

Oral chaperone therapy is a treatment that may overcome the limitations of ERT by stabilising GAA and thus restoring its normal function.8 

Gene therapy is an alternative treatment that targets the genes involved in the production of GAA directly. This option, however, is associated with a risk of immunotoxicity caused by development of anti-GAA antibodies and high dose of vectors.8 

Diagnosis of pompe disease 

Pompe disease is diagnosed based on clinical presentation that confirm the deficiency of GAA enzyme activity: analysis of skin cells and dried blood spots (DBS), and screening for the GAA genetic mutation.5  

DBS is a common and inexpensive test that measures the levels of GAAin the blood. This analysis can be carried out through two different laboratory techniques: a fluorometric method or a mass spectrometry-based method, both of which are suitable for infants. 

The mass spectrometry-based method measures the GAA enzyme activity with higher sensitivity than fluorometry, and has been suggested by the US as a universal newborn screening method for Pompe disease.7 The possibility diagnosis through newborn screening offers a good first step in reducing the timeline of diagnosis.5 


How common is pompe disease?

Pompe disease is classified as a rare genetic disease which affects 1 in 40,000 people. The disease prevalence is, however, higher in African American, Dutch European, and South East Asian populations.3 

Can pompe disease be prevented?

Pompe disease is a genetic disease, which means that it is inherited and cannot be prevented. Nevertheless, the symptoms associated with this condition can be managed and treated.

Who is at risk of pompe disease?

As this is an autosomal recessive disease, hence you need to carry two mutated copies of the gene (one from each parent) to be affected by the disease. Any individual with two affected copies of the gene will therefore develop Pompe disease, though symptoms can arise at any age from infancy to adulthood.

What can I expect if I have pompe disease?

Individuals affected with Pompe disease will show signs and symptoms of muscle weakness and cardiovascular conditions from the first 3 months.3  

When should I see a doctor?

Pompe disease can be diagnosed and detected from early infancy to adulthood.


GSDII is a genetic disorder that affects approximately 1 in 40,000 people and is caused by a mutation in a gene responsible for the production of GAA, which breaks down glycogen into glucose. The accumulation of glycogen as a result of this mutation leads to various symptoms such as muscle deterioration, respiratory difficulties, myopathy, cardiomyopathy, hepatomegaly and feeding and urinary insufficiencies. 

The severity of the condition is impacted by the level of GAA produced, which can vary from the age of onset, according to the rate of disease progression. The infantile onset subtype of this condition affects individuals during the first year after birth and is the most severe form of the condition. Late-onset Pompe disease, on the other hand, is associated with less severe symptoms. Both groups are susceptible to respiratory complications, which represents the leading cause of death associated with this condition. 

The gold standard of diagnosis is dried blood spots (DBS). The diagnosis is inexpensive and simple. Early diagnosis of GSII through newborn screening is beneficial to reduce the diagnosis and treatment timeline. 

Enzyme replacement therapy is an effective treatment for GSDII but has shown limitations such as immunotoxicity. Other alternative treatments to ERT include oral chaperone therapy, modified rhGAA, and autophagy suppression. 


  1. Julie - Pompe disease, knowing is half the battle [Internet]. YouTube. YouTube; 2018 [cited 2023Apr5]. Available from: https://www.youtube.com/watch?v=s26uQufvOxY
  2. Dasouki M, Jawdat O, Almadhoun O, Pasnoor M, McVey AL, Abuzinadah A, et al. Pompe disease: literature review and case series. Neurologic Clinics [Internet]. 2014 Aug 1 [cited 2023 Apr 5];32(3):751–76. Available from: https://www.sciencedirect.com/science/article/pii/S0733861914000334
  3. Pompe disease - symptoms, causes, treatment | nord [Internet]. [cited 2023 Apr 5]. Available from: https://rarediseases.org/rare-diseases/pompe-disease/
  4. van Kooten HA, Roelen CHA, Brusse E, van der Beek N a. ME, Michels M, van der Ploeg AT, et al. Cardiovascular disease in non-classic Pompe disease: A systematic review. Neuromuscul Disord. 2021 Feb;31(2):79–90. Available from: https://www.nmd-journal.com/article/S0960-8966(20)30646-5/fulltext 
  5. Taverna S, Cammarata G, Colomba P, Sciarrino S, Zizzo C, Francofonte D, et al. Pompe disease: pathogenesis, molecular genetics and diagnosis. Aging (Albany NY) [Internet]. 2020 Aug 3 [cited 2023 Apr 5];12(15):15856–74. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467391/
  6. Cupler EJ, Berger KI, Leshner RT, Wolfe GI, Han JJ, Barohn RJ, et al. Consensus treatment recommendations for late-onset pompe disease: aaem practice topic: late-onset pompe disease. Muscle Nerve [Internet]. 2012 Mar [cited 2023 Apr 5];45(3):319–33. Available from: https://onlinelibrary.wiley.com/doi/10.1002/mus.22329
  7. Lukacs Z, Oliva P, Nieves Cobos P, Scott J, Mechtler TP, Kasper DC. At-risk testing for pompe disease using dried blood spots: lessons learned for newborn screening. Int J Neonatal Screen [Internet]. 2020 Dec 21 [cited 2023 Apr 5];6(4):96. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780922/
  8. Kishnani PS, Beckemeyer AA, Mendelsohn NJ. The new era of Pompe disease: Advances in the detection, understanding of the phenotypic spectrum, pathophysiology, and management. Am J Med Genet [Internet]. 2012 Feb 15 [cited 2023 Apr 5];160C(1):1–7. Available from: https://onlinelibrary.wiley.com/doi/10.1002/ajmg.c.31324
  9. Lim JA, Li L, Raben N. Pompe disease: from pathophysiology to therapy and back again. Front Aging Neurosci [Internet]. 2014 Jul 23 [cited 2023 Apr 5];6:177. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135233/
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Suchavadee Liangteva

Masters of Science in Stem Cells & Regenerative Therapies - MSc, King’s College London

Pim is a content creator of Stem Cells research and technologies, with roots in biochemistry and commercialisation of cell and gene therapies. She has a wide range of communications experiences in retail business, life sciences, digital marketing, and working directly with health care providers from Bangkok hospital ER department. She is currently working with University professors and students for guest episodes on her educational podcast and website in stem cells topics called ’Seriously Stem Cells’.

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