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Pompe disease, also known as glycogen storage disease type II, is an autosomal recessive disorder caused by a deficiency of the lysosomal enzyme alpha-glucosidase (GAA) leading to an accumulation of glycogen in the lysosome causing swelling, cell damage, and progressive organ dysfunction. Pompe disease is caused by mutations in the GAA gene, and it is characterized by muscle hypotonia, weakness, cardiomyopathy, and eventually death due to either cardiorespiratory or respiratory failure. The clinical phenotype, in general, appears to be dependent on residual enzyme activity, with complete loss of activity causing onset in infancy leading to death, typically within the first year of life. Juvenile and adult-onset forms are characterized by later onset and longer survival. The estimated incidence is 1 in 40,000 live births.
Enzyme replacement therapy (ERT) improves outcome in many patients with either classic infantile onset or later onset forms of 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 implemented in some states. The early identification and treatment of infants with Pompe disease has been shown to be helpful in reducing the morbidity and mortality associated with this disease.
Since Pompe disease is considered a rare condition that progresses rapidly in infancy, the disease, in particular the juvenile and adult-onset forms, is often considered late, if at all, during the evaluation of patients presenting with muscle hypotonia, weakness, or cardiomyopathy. Testing traditionally required a skin or muscle biopsy to establish cultures for enzyme testing. More recently, molecular genetic testing of the GAA gene (GAAZ / Pompe Disease, Full Gene Analysis) became clinically available. Determination of the enzyme activity in dried blood spot specimens can be performed in a timely fashion and provide better guidance in the decision to submit samples for further confirmatory testing by molecular genetic analysis (GAAZ / Pompe Disease, Full Gene Analysis).
Evaluation of patients of any age with a clinical presentation suggestive of Pompe disease (muscle hypotonia, weakness, or cardiomyopathy)
Normal results (>0.5 nmol/h/mL) in properly submitted specimens are not consistent with classic Pompe disease. Affected individuals typically have levels of 0.5 nmol/h/mL or less; however, some later onset cases may show higher enzyme activity.
Results of 0.5 nmol/h/mL or less can be followed up by molecular genetic analysis of the GAA gene (GAAZ / Pompe Disease, Full Gene Analysis) to determine carrier, pseudodeficiency, or disease status.
Specimens exposed to heat above 25 degrees C for more than 48 hours will yield higher activity levels than properly submitted specimens. This may cause false-normal (false-negative) results in affected patients.
Pseudodeficiency results in low measured GAA, but is not consistent with Pompe disease; GAAZ / Pompe Disease, Full Gene Analysis should be performed to resolve the clinical question.
Normal >0.5 nmol/mL/h
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