Disease Overview

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:

  • Infantile-onset: Infantile-onset Pompe disease (IOPD) is a relentless, severe form of Pompe disease in which infants are usually diagnosed within months of birth and is often fatal within the first year of life. This form is characterized by:
  • Hypotonia (“floppy” appearance) and muscle weakness
  • Cardiomegaly and associated myopathies
  • Respiratory distress
  • Feeding difficulties
  • Failure to thrive
  • Death within the first year of life, typically of cardiorespiratory failure

There are also patients who present with signs and symptoms in infancy without the classic cardiac features of IOPD.

  • Late-onset: Patients with late-onset Pompe disease (LOPD) may present with symptoms after 1 year of age. This phenotype is characterized by a slow progression of symptoms that are initially milder, but increase in severity over time, with infrequent cardiomegaly. Symptoms include:
  • Muscle weakness/stiffness with concomitant strength and mobility issues
  • Elevated creatine kinase (CK)
  • Respiratory insufficiency, sleep apnea, somnolence

Pompe disease may also be included in several broader disease categories such as:

  • Lysosomal storage disorders: There are >50 rare genetic disorders, all of which are caused by the deficiency or malfunction of a particular lysosomal enzyme
  • Glycogen storage diseases: A group of inherited disorders of glycogen metabolism. This classification focuses on the malfunction or lack of enzymes responsible for glycogen storage or degradation, rather than the site of accumulation (lysosome)
  • Pompe disease is the only glycogen storage disease with a concomitant defect in lysosomal metabolism
  • Neuromuscular/metabolic muscle disease: All patients with Pompe share a common disease course resulting from the continual accumulation of glycogen in skeletal muscles, progressive hypotonia, and muscle weakness, classifying Pompe disease as a neuromuscular disease or a metabolic myopathy
  • Cardiac disorders: This classification may be used because of the striking cardiomegaly, cardiomyopathy, and echocardiographic abnormalities seen in the majority of infants with Pompe disease

Pompe disease may be referred to as:

  • Acid maltase deficiency (AMD)
  • Glycogen storage disease type II (GSDII)
  • Acid alpha-glucosidase deficiency
  • Lysosomal alpha-glucosidase deficiency
  • Glycogenosis type II

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:

  • No defect appeared apparent in the glycogen degradation pathway
  • The accumulated glycogen was normal in structure


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.

  • In addition, Hers speculated that other disorders might be explained by faulty or absent lysosomal enzymes and, indeed, Pompe disease was the first identified of >50 lysosomal storage disorders.