What is Pompe disease?

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Pompe disease is a metabolic disorder caused by mutations in the acid alpha-glucosidase (GAA) gene. GAA, an enzyme responsible for breaking down glycogen in the cells, is either absent (resulting in the rapidly progressive infantile form of Pompe disease) or deficient (resulting in the late-onset juvenile or adult form). As a result, glycogen builds up in the lysosomes of cells and tissues, primarily in cardiac and skeletal muscles, affecting their function and causing progressive weakness and organ failure.
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Risk Factors

This is an autosomal recessive disorder; therefore, each parent must carry a defective GAA gene, both of which are inherited by the affected child. The National Institute of Neurological Disorders and Stroke (NINDS) reports (2013) that the incidence is estimated at 1 in 40,000 people worldwide. About one-third of patients have the infantile-onset form. Both sexes are equally affected, although the incidence does vary by geography and ethnic group.

Etiology and Genetics

The GAA gene, located on the long arm of chromosome 17, is the only gene associated with Pompe disease. More than three hundred mutations have been identified throughout the gene. Some defects are more common than others. For example, more than half of Caucasians with late-onset Pompe disease share a common splice-site mutation. According to the Emory University School of Medicine in 2010, some infantile-onset mutations are observed more frequently in certain geographic regions (such as southern China and Taiwan) or ethnic populations (such as African Americans).

In general, the type and combination of mutations inherited determine the residual level of GAA activity and thus the severity of the disease. If both chromosomes are fully compromised, GAA activity is nonexistent. Combinations of one severely mutated allele and one mildly affected allele usually preserve some GAA activity, meaning a slower disease progression, although the age of onset can vary. Researchers are cautious about correlating genotype with clinical features, however, because both infantile and late-onset forms have been observed in the same family.

Several factors explain how glycogen buildup in the lysosomes likely disrupts muscle function. As the lysosomes become bloated, they can displace myofibrils in neighboring cells, disrupting the muscle’s ability to contract and transmit force. In late-onset Pompe disease, swollen lysosomes can rupture or release other enzymes into surrounding tissues, damaging muscles. Disuse and oxidative stress may also play a role in muscle wasting.


Manifestations of Pompe disease vary depending on age of onset and level of residual GAA activity. In the classic infantile-onset form, symptoms are observed shortly after birth and include an enlarged heart, poor muscle tone (inability to hold the head up, roll over), feeding problems (difficulty swallowing, enlarged tongue), and respiratory distress (frequent lung infections). In the nonclassic infantile form, cardiac involvement is moderate and muscle weakness is delayed. In late-onset Pompe disease, symptoms can appear from two to seventy years. Muscle weakness and pain, primarily in the legs and trunk (difficulty climbing stairs or playing sports, frequent falls) and respiratory distress (shortness of breath, sleep apnea) are typical. In all cases, early diagnosis is critical for disease management.

Screening and Diagnosis

Pompe disease shares many symptoms with other muscle disorders, complicating diagnosis. Initial clinical studies include chest radiography and electrocardiograms, as well as muscle tests, electromyography, and nerve conduction tests in adults. The diagnosis is confirmed through tests of GAA activity (blood tests, skin fibroblasts cultures, and/or muscle biopsy in adults) or through DNA analysis. DNA analysis is also useful for identifying familial mutations and carriers and for newborn screening.

Treatment and Therapy

Historically, patients with Pompe disease were given supportive care only. However, enzyme replacement therapy (ERT) using recombinant human GAA has become a promising treatment, especially in infants younger than six months who do not yet require ventilatory assistance. As reported by the National Center for Biotechnology Information (2012), clinical trials of ERT in late-onset Pompe disease are ongoing and also show promise. Other treatment is multidisciplinary and aimed at preventing secondary complications such as infections, treating symptoms, and maintaining function as long as possible. These treatments include frequent cardiac evaluations, use of bronchodilators, steroids, and mechanical ventilation, and special diets and tube feeding. Physical, occupational, and speech therapies and immunizations are also advised.

Prevention and Outcomes

Before ERT, patients with infantile-onset Pompe disease typically died of cardiac and/or respiratory complications by one year of age. ERT has enhanced ventilator-free survival for many young patients; reduced heart size and improvements in cardiac and skeletal muscle function have also been seen. In late-onset Pompe disease, juvenile patients are usually more severely affected than adults and rarely survive past the second or third decade of life due to respiratory failure. They often require mechanical ventilation and wheelchairs. Older patients may also experience steadily progressive debilitation and premature mortality. However, improved screening techniques that enhance early diagnosis have become available. NINDS (2013) reports that not only ERT, but new drugs show promise for treatment.


Acton, Q. Ashton, ed. Pompe's Disease: New Insights for the Healthcare Professional. Atlanta: ScholarlyEditions, 2012. Print.

Anand, Geeta. The Cure: How a Father Raised $100 Million—And Bucked the Medical Establishment in a Quest to Save His Children. New York: Harper, 2006. Print.

Hirschhorn, R., and A. J. Reuser. “Glycogen Storage Disease Type II: Acid Alpha-glucosidase (Acid Maltase) Deficiency.” The Metabolic and Molecular Bases of Inherited Disease. Ed. Charles Scriver, et al. 8th ed. New York: McGraw, 2001. Print.

Hoffman, Georg F., et al. Inherited Metabolic Diseases. New York: Springer, 2010. Print.

Kishnani, Priya S., et al. “Pompe Disease Diagnosis and Management Guidelines.” Genetics in Medicine 8.5 (2006): 267–88. Print.

"Pompe Disease." Genetics Home Reference. Natl. Lib. of Medicine, 4 Aug. 2014. Web. 6 Aug. 2014.

Websites of Interest

Acid Maltase Deficiency Association (AMDA) . http://www.amda-pompe.org/

Association for Glycogen Storage Disease . http://www.agsdus.org/

Pompe Disease . http://ghr.nlm.nih.gov/condition=pompedisease

Pompe Registry . http://www.lsdregistry.net/pomperegistry/

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