Glycogen storage disease type II (also called Pompe disease or acid maltase deficiency) is an autosomal recessivemetabolic disorder which damages muscle and nerve cells throughout the body. It is caused by an accumulation of glycogen in the lysosome due to deficiency of the lysosomal acid alpha-glucosidase enzyme. It is the only glycogen storage disease with a defect in lysosomal metabolism, and the first glycogen storage disease to be identified, in 1932.
The build-up of glycogen causes progressive muscle weakness (myopathy) throughout the body and affects various body tissues, particularly in the heart, skeletal muscles, liver and nervous system.
Pompe disease is a rare, inherited and often fatal disorder that disables the heart and muscles. It is caused by mutations in a gene that makes an enzyme called alpha-glucosidase (GAA). Normally, the body uses GAA to break down glycogen, a stored form of sugar used for energy. But in Pompe disease, mutations in the GAA gene reduce or completely eliminate this essential enzyme. Excessive amounts of glycogen accumulate everywhere in the body, but the cells of the heart and skeletal muscles are the most seriously affected. Researchers have identified over 300 different mutations in the GAA gene that cause the symptoms of Pompe disease, which can vary widely in terms of age of onset and severity.
Incidence & Prevalence
An analysis in early 2024 used NBS data from more than 11 million newborns, screened across eight countries between 2010 and 2022. It found the birth prevalence of Pompe to be 1 in 18,711, or 5.3 cases of Pompe for every 100,000 births. Researchers believe this estimate is conservative, as it only accounts for cases captured via NBS at birth.
Determining the exact Pompe disease prevalence is difficult because it’s a rare condition that can be challenging for doctors to accurately diagnose. But with advances in newborn screening programs (NBS) that test babies for rare genetic diseases at birth, scientists are starting to get a better picture of how many people are living with the neuromuscular condition.
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.
Martiniuk F, Chen A, Mack A, et al. Carrier frequency for glycogen storage disease type II in New York and estimates of affected individuals born with the disease. Am J Med Genet 1998; 79: 69-72.
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.