Related Diseases
Pompe

Types and Symptoms

Causes

Inheritance

Testing

Treatment/Management

Additional Information Links

Glycogen storage disease type II (GSDII), also known as acid maltase deficiency (AMD), acid a-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. Since that time, a great deal has been learned about the biochemical and genetic bases of GSDII. Both carrier testing and prenatal diagnosis are available for at-risk families, and recently researchers have been investigating new therapies.

Types and Symptoms

Pompe disease is a continuum of types of glycogen storage disease 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, 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 1 or 2 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 2 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 2 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 for decades with supportive treatment.

Causes

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 a-glucosidase (also known asacid-maltase). Acid a-glucosidase is normally present in the lysosomes and is necessary for the metabolism of glycogen back to glucose. When acid µ-glucosidase is deficient, the excess glycogen accumulates in all tissues, but particularly in the lysosomes of skeletal and cardiac muscle. This leads to the muscle weakness and other symptoms of GSDII. Infants with GSDII have almost no acid a-glucosidase enzyme activity, whereas individuals with juvenile or adult-onset GSDII have reduced enzyme activity.

Inheritance

GSDII is inherited as an autosomal recessive trait. Both of the parents of an affected individual are carriers of an altered gene on chromosome 17, which is responsible for producing acid a-glucosidase. A parent who is a carrier is healthy because he or she has one functional copy of the gene which produces a sufficient amount of the enzyme. An individual who inherits two altered copies of the gene, one from each parent, will either produce no acid a-glucosidase or will produce a significantly reduced amount. The severity of the disease and age of onset depend on the amount of functional acid a-glucosidase that an individual is able to produce.

All forms of GSDII are pan-ethnic, but the frequency may differ among groups. For example, in Southern China and Taiwan the frequency of infantile-onset GSDII is estimated to be 1 in 50,000, and among African-Americans may be as high as 1 in 14,000. In the Dutch population the frequency of infantile-onset GSDII is estimated to be 1 in 138,000; however the frequency of adult-onset GSDII among the Dutch is estimated to be 1 in 57,000. The overall incidence of the disease is not known, but among Caucasian populations the frequency of infantile-onset GSDII is mostly likely 1 in 100,000 to 1 in 200,000.

Testing

Testing to confirm a diagnosis of GSDII is performed most reliably by measuring the acid a-glucosidase enzyme activity in muscle or skin biopsies. Prenatal diagnosis is possible by determining enzyme activity in amniotic cells obtained via amniocentesis, or chorionic villus biopsies obtained via chorionic villus sampling (CVS). In families or individuals with a known history of GSDII, DNA msutation analysis may provide additional information, and may enable carrier testing in family members. Many different mutations have been identified in the gene for acid a-glucosidase, but most occur in only one or two families. A few mutations seem to be more frequent among particular ethnic groups, for example in Africans and African- Americans. Additional research will no doubt lead to the identification of more mutations and a better understanding of the correlation between specific mutations and the resulting severity/age of onset of GSDII disease.

Treatment/Management

In April 2006 Myozyme ®, an enzyme replacement therapy became commercially available for the treatment of Pompe. Myozyme has been shown to improve ventilator-free survival in patients with infantile-onset Pompe disease as compared to an untreated historical control, whereas use of Myozyme in patients with other forms of Pompe disease has not been adequately studied to assure safety and efficacy. To learn more visit www.Myozyme.com.

 

 

 

 

 

Additional Informational Links

The following online resources may be helpful in learning more about Pompe Disease: