Clinical Information

Pompe disease, also known as glycogen storage disease type II, is an autosomal recessive disorder caused by a deficiency of the lysosomal enzyme, acid alpha-glucosidase (GAA). This leads to an accumulation of glycogen in the lysosome causing swelling, cell damage, and progressive organ dysfunction. In glycogen storage diseases, excess glycogen is degraded to glucotetrasaccharide (glucose tetrasaccharide: Glc4), which is excreted in urine. Measurement of Glc4 in urine is used for both initial diagnosis and monitoring of patients with Pompe disease and may also be elevated in other glycogen storage disorders.

Pompe disease is caused by deleterious variants in the GAA gene. The classic, early infantile onset form of the disease is characterized by progressive muscle hypotonia, weakness, hypertrophic cardiomyopathy, and death due to either cardiorespiratory or respiratory failure, typically by the end of the first year of life. Juvenile and adult-onset forms of Pompe disease are characterized by later onset and longer survival. Primary symptoms of later-onset Pompe disease include muscle weakness and respiratory insufficiency, with cardiomyopathy only rarely developing. Based on data from newborn screening, the incidence is approximately 1 in 20,000 live births with most patients being affected with later onset forms of Pompe disease. The clinical phenotype depends on residual enzyme activity, with complete loss of activity causing onset in infancy.

Enzyme replacement therapy (ERT) improves outcomes in many patients with either classic infantile-onset or later-onset Pompe disease. Early initiation of treatment improves the prognosis and makes early diagnosis of Pompe disease desirable. Because of this, newborn screening for Pompe disease has recently been added to the Recommended Uniform Screening Panel and already been implemented in some states.

Historically, diagnostic testing required a skin or muscle biopsy to measure GAA enzyme activity. Today, noninvasive enzyme assays (GAAW / Acid Alpha-Glucosidase, Leukocytes) and molecular genetic analysis of the GAA gene (GAAZ / Pompe Disease, Full Gene Analysis, Varies) are available for testing in blood and dried blood spots. In addition, Glc4 can be measured in urine to support a diagnosis of Pompe disease and other glycogen storage disorders.