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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. Treatment by enzyme replacement therapy, recently available, makes early diagnosis of Pompe disease desirable, as early initiation of treatment may improve the prognosis. The estimated incidence is 1 in 40,000 live births.
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, and/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 assay 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, and/or cardiomyopathy)
Normal results (>7.4 pmol/dried blood spot punch/hour) in properly submitted specimens are not consistent with classic Pompe disease. Affected individuals typically show <2.5 pmol/dried blood spot punch/hour; however, some later onset cases may show higher enzyme activity.
Results <7.5 pmol/dried blood spot punch/hour can be followed up by molecular genetic analysis of the GAA gene (GAAZ / Pompe Disease, Full Gene Analysis) to determine carrier or disease status.
Specimens exposed to heat >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.
Normal >7.4 pmol/punch/h
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2. Winkel LP, Hagemans ML, van Doorn PA, et al: The natural course of non-classic Pompe's disease; a review of 225 published cases. J Neurol 2005;252:875-884
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