Pompe disease is a progressive, multisystemic, debilitating, and often fatal neuromuscular disorder.
Pompe disease is estimated to affect 1 in 40,000 in the U.S. with a genetic carrier frequency estimated at 1 in 100.
In 1931, the pathologist Johannes C. Pompe first described a case of the death of a 7-month-old infant with “idiopathic hypertrophy of the heart,” consisting of greatly thickened walls and chambers but normal valves. This, and a series of important observations that followed, led to the characterization of Pompe disease.
Pompe disease is a single disease with great phenotypic variation. To be more consistent with disease terminology, Pompe disease may be classified into several phenotypes:
There are also patients who present with signs and symptoms in infancy without the classic cardiac features of IOPD.
Pompe disease may also be included in several broader disease categories such as:
Pompe disease may be referred to as:
Timeline of the Discovery and Characterization of Pompe Disease
Johannes Pompe noticed histologically that the cardiac muscle fibers were nearly unrecognizable due to large vacuoles filled with glycogen (carmine staining). Pompe made the critical observation that these glycogen-filled vacuoles were also present in other tissues including the liver, kidneys, and skeletal muscle.
The delineation of the normal pathway for glycogen metabolism by Gerty T. Cori and Carl F. Cori allowed for the characterization of the metabolic basis of Pompe disease, and other similar cases, and for their classification as glycogen storage diseases (GSDs). Pompe disease was the most severe of these GSDs and classified as type II (GSDII). Two other important observations were made regarding Pompe disease:
de Duve and colleagues identified the lysosome as an intracellular membrane-bound organelle containing hydrolytic enzymes that are stable and active at acidic pH, and capable of hydrolyzing various bonds and breaking down macromolecules.
Hers and colleagues made the seminal discovery of the intralysosomal enzyme alpha glucosidase (also referred to as acid maltase, acid alpha-glucosidase, or GAA), which is capable of releasing glucose from glycogen (or from maltose). Most important, they also discovered that this enzyme was absent from infants diagnosed with Pompe disease.