Pompe Disease (Glycogen Storage Disease Type II)

Glycogen storage disease type II (GSDII), also known as acid maltase deficiency, acid alpha-glucosidase deficiency, or Pompe disease, was originally named for Joannes Cassianus Pompe, a Dutch pathologist who was among the first to describe the condition in 1932. Pompe disease is a continuum of types of glycogen storage diseases that vary in severity and the age of first symptoms.  The most severe form, described by Pompe, is referred to as classic infantile-onset GSDII. Symptoms begin within the first few months of life and include marked hypotonia (abnormally severe loss of muscle tone), progressive muscle weakness and cardiomegaly (an enlarged and thickened heart). Feeding and respiratory problems due to congestive heart failure are often among the earliest symptoms. The disease progresses rapidly and most infants die before the age of one or two years due to respiratory or cardiac failure.
 
There is also a non-classic infantile form of GSDII, in which the muscular symptoms occur without pronounced cardiomegaly. Some of these infants may survive beyond the age of two years. The childhood or “juvenile” onset form of GSDII is more slowly progressive than the infantile forms of the disease.  Symptoms generally begin after early infancy but can be quite variable.  Among children whose symptoms begin after the age of two years, the majority have muscular symptoms but not cardiomegaly. Death usually occurs by the age of 30 due to respiratory failure. An adult-onset form of GSDII may occur as late as the sixth decade of life. Symptoms include slowly progressive muscle weakness and/or respiratory difficulties, but not cardiomegaly. Individuals with the adult-onset form generally die due to respiratory failure, but may survive decades with supportive treatment.
 
GSDII is one of several glycogen storage disorders caused by abnormalities in the metabolism of glycogen but GSDII is distinct from other forms in that glycogen accumulates inside the lysosomes of the cell rather than outside.  GSDII results from a deficiency in the enzyme acid alpha-glucosidase (also known as acid maltase). Acid alpha-glucosidase is normally present in the lysosomes and is necessary for the metabolism of glycogen back to glucose.  When acid alpha-glucosidase is deficient, the excess glycogen accumulates in all tissues, but particularly in the lysosomes of skeletal and cardiac muscle. This leads to muscle weakness and other symptoms of GSDII. Infants with GSDII have almost no enzyme activity, whereas individuals with juvenile or adult-onset GSDII have reduced enzyme activity.