Acid Alpha-Glucosidase, Blood Spot

CPT CODE:

USEFUL FOR:

Evaluation of patients of any age with a clinical presentation suggestive of Pompe disease (muscle hypotonia, weakness, and/or cardiomyopathy)

SPECIMEN REQUIRED:

2 blood spots from Whatman 903 filter paper is preferred (Mayo "Newborn Screening Card [Supply T493] is also acceptable). Letblood dry on the filter paper at ambient temperature in a horizontalposition for 3 hours.  An alternative blood collection option forpatients >1 year of age is fingerstick. Note:    1. Do not expose specimen to heat or direct sunlight.             2. Do not stack wet specimens.             3. Do not use devices or capillary tubes containing EDTA                  to collect specimen.             4. Keep specimen dry.

TRANSPORT TEMPERATURE:

Ambient\Refrig NO\Frozen NO

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 alpha-glucosidase (GAA) due to mutations in the GAA gene. The estimated incidence is 1 in 40,000 live births. In Pompe disease, glycogen that is taken up by lysosomes during physiological cell turnover accumulates, causing lysosomal swelling, cell damage, and eventually organ dysfunction. This leads to progressive muscle weakness, cardiomyopathy, and eventually death. The clinical phenotype appears to be dependent on residual enzyme activity, with complete loss causing onset in infancy leading to death, typically within the first year of life. Juvenile and adult-onset forms, as the names suggest, are characterized by later onset and longer survival. Treatment by enzyme replacement therapy became available recently, making early diagnosis of Pompe disease desirable, as early initiation of treatment may improve prognosis.
Because Pompe disease is considered a rare condition that progresses rapidly in infancy, the disease, in particular the juvenile and adult-onset forms, are often considered late, if at all, during the evaluation of patients presenting with muscle hypotonia, weakness, and/or cardiomyopathy. Testing traditionally required a skin biopsy to establish fibroblast cultures or a muscle biopsy for enzyme testing. More recently, molecular genetic testing of the GAA gene became clinically available. However, all of these studies are expensive, which may further contribute to the late diagnosis of affected patients. 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.

CLINICAL INTERPRETATION:

Normal results (>7.4 pmol/dried blood spot punch/hour) in properly submitted specimens are not consistent with Pompe disease. The range seen in unaffected carriers is 2.5 to 7.4 pmol/dried blood spot punch/hour. Affected individuals show <2.5 pmol/dried blood spot punch/hour.
Results <7.5 pmol/dried blood spot punch/hour can be followed up by molecular genetic analysis of the GAA gene to determine carrier status or disease status.

REFERENCE VALUES:

Normal >7.4 pmol/punch/hr