Signs and Symptoms in Children & Adults with Pompe Disease

It took almost 30 years after Pompe disease was first described in infants before it began to be identified in older patients. This delay was likely due to the wide variability in age of onset and clinical presentations, and the fact that many signs and symptoms are not unique to Pompe disease. Today, the diagnosis of Pompe disease continues to be challenging for the same reasons.

While proximal and limb-girdle muscle weakness and respiratory difficulties are typical, exactly how these manifest can vary widely. Symptoms are often heterogeneous, non-specific and easily confused with other disorders. The cardiac involvement that is common in infants is very rare among children and adults.[1]

See the comprehensive signs and symptoms list

Initial Presentation

When Pompe disease presents in children or adults, the predominant sign is usually progressive muscle weakness, generally beginning with the trunk and proximal muscles of the lower limbs.[1], [2] Clinical manifestations can first appear at any age, from early childhood to late adulthood. In children, the first signs may be delayed motor milestones.[1], [2] Similarly, adults may first notice difficulty walking or climbing stairs and exhibit gait abnormalities.

Early respiratory involvement resulting from degeneration of the diaphragm and other respiratory muscles may manifest as respiratory insufficiency, including orthopnea and indications of sleep-disordered breathing such as morning headaches and daytime fatigue.[4]

See the signs and symptoms list (below)

Ongoing Progression

Although the rate of progression varies among patients, Pompe disease is always relentlessly progressive. Many individuals eventually require ambulatory and ventilation support.[2], [4],[7-9]

  • Weakness of hip muscles leads to difficulty walking, climbing stairs, rising from the floor, and often loss of ambulation[2-3], [4], [5]
  • Impaired respiratory muscles lead to respiratory insufficiency, sleep-disordered breathing, and eventual need for mechanical ventilation[1], [2], [6], [7-9]
  • Weakened spinal muscles often cause lordosis, kyphosis, or scoliosis[1]
  • Progressive respiratory insufficiency can ultimately result in premature death from respiratory failure[1]

In general, outcomes are difficult to predict because the disease course is often variable. Some patients may experience relatively mild symptoms for years, followed by an abrupt clinical decline, which can occur at any time.

Older children & adults symptom interactive

Comprehensive Signs & Symptoms List

Following is a detailed list of possible signs and symptoms that may appear in children, adolescents, and adults with Pompe disease.[1], [6], [10-14]


  • Progressive proximal muscle weakness (trunk and lower limbs)
  • Gait abnormalities
  • Muscle pain
  • Difficulty climbing stairs
  • Frequent falls
  • Scapular winging
  • Difficulty chewing or jaw muscle fatigue


Respiratory complications are caused by weakening of the diaphragm and other respiratory muscles.

  • Respiratory failure
  • Orthopnea
  • Exertional dyspnea
  • Respiratory tract infections
  • Daytime somnolence
  • Morning headache
  • Nocturnal hypoventilation


  • Creatine kinase (CK) levels normal to elevated, with or without symptoms
  • Arrhythmias may be present


  • Feeding and swallowing difficulties
  • Poor weight gain/maintenance

More Details: Quality of Life Impact

Pompe disease’s relentless progression can be very debilitating. The resulting physical disabilities place a considerable burden on patients’ quality of life, limiting mobility, independence and self-care.[2-3]

Find out more about Pompe disease’s impact on patient quality of life


  1. Hirschhorn, Rochelle and Arnold J. J. Reuser. Glycogen Storage Disease Type II: Acid Alpha-glucosidase (Acid Maltase) Deficiency. In: Scriver C, Beaudet A, Sly W, Valle D, editors. The Metabolic and Molecular Bases of Inherited Disease. 8th Edition. New York: McGraw-Hill, 2001. 3389-3420.
  2. Hagemans ML, Winkel LP, Hop WC, Reuser AJ, Van Doorn PA, Van der Ploeg AT. Disease severity in children and adults with Pompe disease related to age and disease duration. Neurology 2006; 64:2139-41.
  3. Haley SM, Fragala MA, Skrinar AM. Pompe disease and physical disability. Dev Med Child Neurol 2003; 45:618-23.
  4. Hagemans ML, Winkel LP, Van Doorn PA, et al. Clinical manifestation and natural course of late-onset Pompe’s disease in 54 Dutch patients. Brain 2006; 128:671-7.
  5. Hagemans ML, Hop WC, Van Doorn PA, Reuser AJ, Van der Ploeg AT. Course of disability and respiratory function in untreated late-onset Pompe disease. Neurology 2006; 66:581-3.
  6. Winkel LP, Hagemans ML, van Doorn PA, et al. The natural course of non-classic Pompe’s disease; a review of 225 published cases. J Neurol 2006; 252:875-84.
  7. Kishnani PS, Steiner RD, Bali D, et al. Pompe disease diagnosis and management guideline. Genet Med 2006; 8:267-88.
  8. Bembi B, Cerini E, Danesino C, et al. Diagnosis of glycogenosis type II. Neurology. 2008;71(23 Suppl 2):S4-11.
  9. Oba-Shinjo S, da Silva R, Andrade F, et al. Pompe disease in a Brazilian series: clinical and molecular analyses with identification of nine new mutations. J Neurol 2009;256(11):1881-90. Epub 2009 Jul 9.
  10. Ausems MG, Verbiest J, Hermans MP, et al. Frequency of glycogen storage disease type II in The Netherlands: implications for diagnosis and genetic counseling. Eur J Hum Genet 1999 Sep; 7(6): 713-6.
  11. Kishnani PS, Hwu W-L, Mandel H, Nicolino M, Yong F, Corzo D. A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. J Pediatr 2006; 148:671-676.
  12. Van den Hout HMP. The natural course of infantile Pompe’s disease: 20 original cases compared with 133 cases from the literature. Pediatr 2003 Aug; 112 (2): 332-340.
  13. King, Frank J. Acid Maltase Deficiency Myopathy. eMedicine Specialties. Available at: Accessed 10/23/09.
  14. Mellies U, Ragette R, Schwake C, et al. Sleep-disordered breathing and respiratory failure in acid maltase deficiency. Neurology 2001 Oct 9; 57(7): 1290-5.

Ask a Medical Question

Genzyme Medical Information can answer questions about Pompe disease.

Ask a Question

Genzyme Support Services

Learn how Genzyme can help people affected by Pompe disease with medical information, advocacy, treatment support, and more.

Learn More

Pompe Registry

Find out about the Pompe Registry, an ongoing, observational database that tracks natural history and outcomes of patients with Pompe disease.

Learn More