About Pompe Disease
What is Pompe disease?
Pompe disease is a debilitating, progressive, multi-system genetic disorder affecting an estimated 1 in 40,000 people.1,2,3
Classed as both a glycogen storage and lysosomal storage disease,2 it is caused by an autosomal recessive mutation in the GAA gene for acid α-glucosidase4,1 and results in harmful accumulation of glycogen in the tissues, particularly skeletal, smooth and cardiac muscle.5
There are almost 600 known GAA mutations, resulting in different degrees of enzyme impairment,5 and two key clinical phenotypes, infant-onset (IOPD; usual presentation ≤1 year) and late-onset (LOPD; typical presentation in children over 1 year, but may present as late as the sixth decade).1,2,3
Presentation of LOPD is heterogeneous, with a variable age of onset and symptoms often associated with other conditions, so patients may remain undiagnosed for many years.2,3,5,7
As it progresses, LOPD significantly affects physical and mental health and quality of life for patients and their carer(s).8,9 Progressive loss of muscle strength and function may eventually result in respiratory failure, the most common cause of death.1,2,3
Symptoms of Pompe disease
The main symptoms of IOPD are severe muscle hypotonia, cardiomyopathy and respiratory insufficiency.3,2 Left untreated, most infants die within their first year, often as a result of cardiac or respiratory failure.6,1
Early signs of LOPD include myalgia, exercise intolerance and fatigue, which may be attributed to behavioural reluctance to exercise or other conditions.3,6 Pompe disease can affect any body system, with gastrointestinal, cardiac, respiratory, neurological and musculoskeletal symptoms commonly seen.2,6
Pompe disease symptoms affecting different organ systems
Typical course of late-onset Pompe disease (LOPD)
- Myalgia3
- Fatigue3
- Exercise intolerance3,6
- Skeletal muscle lose strength (lower limbs before upper)1,3
- Compensory patterns of movement and posture6
- Osteopenia or osteopororis6
- Impaired respiration function, particulary apparent when lying down and sleeping3,6
- Dependent on wheelchair1,3
- Often require assisted ventilation1,3
- Respiratory failure common cause of death3,6
Diagnosing Pompe disease
Early diagnosis and treatment are critical for delaying permanent organ damage.4
About 95% of LOPD patients have elevated serum CK, and this combined with classic symptoms can be an early indicator.2,3 The diagnostic flow for confirmation of the condition is shown in this diagram.
Typical late-onset Pompe disease diagnostic pathway
Other alternative clinical routes
can be taken. For example:
- Lung function and muscle strength tests2
- MRI to visualise the degree of muscle damage5
- Muscle biopsy – histology and histochemistry2
References
- Lim JA, Li L, Raben N. Pompe disease: from pathophysiology to therapy and back again. Front Aging Neurosci. 2014;6:177.
- Kishnani PS, Steiner RD, Bali D, et al. Pompe disease diagnosis and management guideline. Genet Med. 2006;8(5):267–288.
- Toscano A, Rodolico C, Musumeci O. Multisystem late onset Pompe disease (LOPD): an update on clinical aspects. Ann Transl Med. 2019;7(13):284.
- Fisher R, Love-Nichols J. Pompe Disease Family Education Booklet. Division of Pediatric Genetics Metabolism and Genomic Medicine, University of Michigan. 2017. http://www.med.umich.edu/1libr/Pediatrics/Genetics/PompeDiseaseBooklet.pdf. Accessed November 2025
- National Organization for Rare Disorders. Pompe disease. January 2024. Available at: https://rarediseases.org/rare-diseases/pompe-disease/. Accessed November 2025.
- Kishnani PS, et al. Late-Onset Pompe Disease: Presentation, Diagnosis and Management. A CME Monograph. American Association of Neuromuscular & Electrodiagnostic Medicine and MedLogix Communications, LLC.
- Kohler L, Puertollano R, Raben N. Pompe disease: from basic science to therapy. Neurotherapeutics. 2018;15: 928-942.
- Schoser B, Bilder DA, Dimmock D, et al. The humanistic burden of Pompe disease: are there still unmet needs? A systematic review. BMC Neurol. 2017;17:202.
- Hagemans MLC, Janssens ACJW, Winkel LPF, et al. Late-onset Pompe disease primarily affects quality of life in physical health domains. Neurol. 2004;63:1688-1692.