Understanding Pompe Disease

Pompe disease, also known as glycogen storage disease type II and acid maltase deficiency (AMD), is both a glycogen storage and lysosomal storage disease caused by a defect in the GAA gene. The faulty GAA gene results in the absence or significant deficiency of an important enzyme called acid alpha-glucosidase (GAA). GAA is required by the body to break down a complex sugar (glycogen) into a simple sugar (glucose) to be used as fuel and energy for cells.1 Due to the lack of GAA enzyme, glycogen accumulates in tissues primarily affecting skeletal and cardiac muscle. In individuals living with Pompe disease, as glycogen accumulates, muscles become progressively weaker causing the wide range of disease symptoms in patients of all ages.

Classic infantile-onset Pompe disease affects infants during the first year of life and follows an aggressive disease course including an enlarged heart (cardiomyopathy) and a ‘floppy baby’ appearance indicative of severe muscle weakness. Infantile-onset Pompe disease is associated with a rapid progression of disease severity and a high mortality rate.3

Late-onset Pompe disease typically affects patients greater than one year of age through adulthood. The disease course is slower than seen in infantile-onset; regardless, it is a relentless and progressive disease with a significantly increased mortality rate. The muscles most affected in late-onset Pompe disease are those closest to the midline of the body (proximal muscles) including the muscles of the legs, thighs, upper arms and shoulders. Proximal muscle weakness may eventually lead to the inability to walk independently and the need for a wheelchair. Additionally, pulmonary involvement includes the diaphragm and results in breathing difficulties like shortness of breath and frequent respiratory infections, which impact everyday quality of life.1  

How is Pompe Disease Inherited?

Pompe disease is inherited in an autosomal recessive manner. Normally, a person has two working copies of the gene that provides the instruction code for making the GAA enzyme. When a person has one normal gene and one faulty gene they are a “carrier” for Pompe disease and do not develop the disease. When two carrier parents have children, each parent will pass one of their genes (either the normal gene or the faulty gene) to their child. With each pregnancy, two carrier parents have a 25% chance of having an unaffected child, a 1 in 2 (50%) chance of having a carrier child, and a 1 in 4 chance (25%) of having a child affected by Pompe disease. Males and females are equally affected.

How Common is Pompe Disease?

The incidence of Pompe disease is higher than suggested in the past. In the United States, the prevalence of Pompe disease is approximately 1 in 28,000. It is estimated that approximately one-third of those with Pompe disease have the infantile-onset form, while the majority of patients have the late-onset form.5

Patient-Friendly Links

The following links provide additional patient-friendly information on Pompe disease:

ACMG Work Group on Management of Pompe Disease:, Kishnani PS, Steiner RD, et al. Pompe disease diagnosis and management guideline. 
Genetics in Medicine. 2006;8(5):267-288. doi:10.1097/01.gim.0000218152.87434.f3.

2 Hirschhorn R et al. 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, 3389-3420 (2001)

3 Case LE et al. Infantile Pompe disease on ERT: update on clinical presentation, musculoskeletal management, and exercise considerations.
Am J Med Genet C Semin Med Genet. 160C:69–79 (2012).

4 National Organization for Rare Diseases (NORD)
www.rarediseases.org/Pompedisease. Accessed August 2017.

5 Kemper AR. The Condition Review Workgroup. Evidence Report: Newborn Screening for Pompe Disease (2013). http://www.hrsa.gov/advisorycommittees/mchbadvisory/heritabledisorders/nominatecondition/reviews/pompereport2013.pdf. Accessed August 2017.