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Test Code GAABS Acid Alpha-Glucosidase, Blood Spot

Reporting Name

Acid Alpha-Glucosidase, BS

Useful For

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

Testing Algorithm

See Newborn Screen Follow-up for Pompe Disease in Special Instructions.

 

For more information, see Newborn Screening Act Sheet Pompe Disease: Decreased Acid Alpha-Glucosidase in Special Instructions.

Method Name

Fluorometric Enzyme Assay

Performing Laboratory

Mayo Medical Laboratories in Rochester

Specimen Type

Whole blood


Additional Testing Requirements


Molecular genetic testing of the GAA gene (GAAZ / Pompe Disease, Full Gene Analysis) can be used to determine carrier, pseudodeficiency, or disease status.

 

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.



Necessary Information


Provide a reason for referral and clinical indication with each specimen.



Specimen Required


Supplies: Card-Blood Spot Collection (Filter Paper) (T493)

Container/Tube:

Preferred: Blood spot collection card (T493)

Acceptable: Ahlstrom 226 Filter Paper, Munktell TFN, and Whatman Protein Saver 903 Paper

Specimen Volume: 2 blood spots

Collection Instructions:

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.

Additional Information:

1. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777) in Special Instructions.

2. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800) in Special Instructions.


Specimen Minimum Volume

1 blood spot

Specimen Stability Information

Specimen Type Temperature Time
Whole blood Ambient (preferred) 87 days
  Frozen  87 days
  Refrigerated  87 days

Reject Due To

Hemolysis

NA

Lipemia

NA

Icterus

NA

Other

Blood spot specimen that shows serum rings or has multiple layers

Reference Values

Normal >0.5 nmol/mL/hour

Day(s) and Time(s) Performed

Varies

CPT Code Information

82657

LOINC Code Information

Test ID Test Order Name Order LOINC Value
GAABS Acid Alpha-Glucosidase, BS In Process

 

Result ID Test Result Name Result LOINC Value
30100 Reason For Referral 42349-1
30149 Acid alpha-glucosidase 55827-0
30102 Interpretation (GAABS) 59462-2
30104 Reviewed By No LOINC Needed

Specimen Retention Time

1 year

Method Description

Whole blood is collected on a blood spot collection card 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 ambient temperatures. 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. The plate is sealed with aluminum sealer and incubated at 37° C for 20 hours. Then, 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)

Analytic Time

8 days

Cautions

Specimens exposed to heat above 25° 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.

Interpretation

Normal results (>0.5 nmol/hour/mL) in properly submitted specimens are not consistent with classic Pompe disease. Affected individuals typically have levels of 0.5 nmol/hour/mL or less; however, some later onset cases may show higher enzyme activity.

 

Results of 0.5 nmol/hour/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.

Test Classification

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.

Forms

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 (T576) is available in Special Instructions.

2. Biochemical Genetics Patient Information (T602) in Special Instructions

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). This leads 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, cardiomegaly, hypertrophic cardiomyopathy, and eventual 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. Untreated, this leads to death, typically within the first year of life. Juvenile and adult-onset forms are characterized by later onset and longer survival. Primary symptoms of later-onset Pompe disease include muscle weakness and respiratory insufficiency. Rarely, clinically significant cardiomyopathy can be seen. 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 proximal muscle weakness and respiratory insufficiency. 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).