Acid Alpha-Glucosidase, Blood Spot
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Evaluation of patients of any age with a clinical presentation suggestive of Pompe disease (muscle hypotonia, weakness, and/or cardiomyopathy)
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Fluorometric Enzyme Assay
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Acid Alpha-Glucosidase, BS
Acid Maltase Deficiency
Glycogen Storage Disease Type II (GSD II)
Acid Maltase Deficiency
Glycogen Storage Disease Type II (GSD II)
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Preferred: Whatman Protein Saver 903 Paper
Acceptable: Ahlstrom 226 Filter Paper, Supplemental Newborn Screening Card (Supply T493)
Specimen Volume: 2 blood spots
1. Do not use device or capillary tube containing EDTA to collect specimen.
2. An alternative blood collection option for a patient >1 year of age is fingerstick.
3. Let blood dry on the filter paper at ambient temperature in a horizontal position for 3 hours.
4. Do not expose specimen to heat or direct sunlight.
5. Do not stack wet specimens.
6. Keep specimen dry.
1. 1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
2. 2. If not ordering electronically, submit a Biochemical Genetics Request Form (Supply T439) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Blood Spot: 1
Blood spot specimen that shows serum rings or has multiple layers
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Whole blood||Ambient (preferred)||87 days|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 (GAAMS/89898 Pompe Disease, Full Gene Sequencing) 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 (GAAMS/89898 Pompe Disease, Full Gene Sequencing).
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Normal >7.4 pmol/punch/h
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 (GAAMS/89898 Pompe Disease, Full Gene Sequencing) to determine carrier or disease status.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
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.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Kishnani PS, Howell RR: Pompe disease in infants and children. J Pediatr 2004;144:S35-S43
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
3. Katzin LW, Amato AA: Pompe disease: a review of the current diagnosis and treatment recommendations in the era of enzyme replacement therapy. J Clin Neuromuscul Dis 2008 Jun;9(4):421-431
4. Enns GM, Steiner RD, Cowan TM: Lysosomal disorders. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth. McGraw-Hill, Medical Publishing Division, 2009, pp 750-751
Method Description Describes how the test is performed and provides a method-specific reference
Whole blood is collected on Protein Saver 903 (Whatman) filter paper and dried at room temperature. A one-eighth inch (3-mm) disk is punched out of the dried blood spots into a microcentrifuge tube. The extraction of blood from the blood spot using water takes place on an orbital shaker for 1 hour at 2 to 8 degrees C in a chilled shaker or cool room. A total of 40 mcL of the extracted sample is combined with 50 mcL of substrate A (40 mM sodium acetate, pH 3.8 with 1.4 mM 4-methylumbelliferyl-alpha-D-glucopyranoside [4-MUG]) and 10 mcL of 8 mcmol acarbose (acts as an inhibitor of leukocyte-derived alpha-glucosidase) in a black 96-well plate, in duplicate. Blanks that contain substrate and inhibitor only are also set up in duplicate with 2 wells used for each patient. The plate is sealed with aluminum sealer and incubated at 37 degrees C for 20 hours. The remaining extracts are also incubated at 37 degrees C for 20 hours. The plate is centrifuged at 600 g for 5 minutes to collect any condensation on the sealer. A total of 40 mcL of the leftover extracts are added to each of the corresponding "blank" wells for each patient. Finally, 200 mcL of stop buffer (150 mM EDTA, pH 11.4) is added to all wells. A calibration curve is set up on every plate to calculate results. (Chamoles NA, Niizawa G, Blanco M, et al: Glycogen storage disease type II: enzymatic screening in dried blood spots on filter paper. Clin Chim Acta 2004;347:97-102; Zhang H, Kallwass H, Young SP, et al: Comparison of maltose and acarbose as inhibitors of maltase-glucoamylase activity in assaying acid alpha-glucosidase activity in dried blood spots for the diagnosis of infantile Pompe disease. Genet Med 2006;8:302-306)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|30100||Reason For Referral||42349-1|