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HelpTest ID: GAAN Pompe Disease, GAA Gene Sequencing with Deletion/Duplication, Varies
Ordering Guidance
Biochemical testing for the diagnosis of Pompe disease should be considered prior to molecular confirmation with this test. Testing options include:
-GAAW / Acid Alpha-Glucosidase, Leukocytes
-For patients older than 6 weeks, PDBS / Pompe Disease, Blood Spot
-For patients 6 weeks and younger, PD2T / Pompe Disease Second-Tier Newborn Screening, Blood Spot
For therapeutic monitoring using urinary glucotetrasaccharide biomarkers, order HEX4 / Glucotetrasaccharides, Random, Urine
Testing for the GAA gene as part of a customized panel is available. See CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies. To modify this panel via CGPH, use the Inborn Errors of Metabolism disease state for step 1 on the Custom Gene Ordering Tool.
Targeted testing for familial variants (also called site-specific or known variants testing) is available for variants identified in the GAA gene. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.
Additional Testing Requirements
All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen as this must be a different order number than the prenatal specimen.
Specimen Required
Patient Preparation: A previous hematopoietic stem cell transplant from an allogenic donor will interfere with testing. For information about testing patients who have received a hematopoietic stem cell transplant, call 800-533-1710
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube: Lavender top (EDTA) or yellow top (ACD)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 4 days/Frozen 4 days
Additional Information:
1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.
2. To ensure minimum volume and concentration of DNA is met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.
Specimen Type: Cord blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send cord blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 4 days/Frozen 4 days
Additional Information:
1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.
2. To ensure minimum volume and concentration of DNA is met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.
3. While a properly collected cord blood sample may not be at risk for maternal cell contamination, unanticipated complications may occur during collection. Therefore, maternal cell contamination studies are recommended to ensure the test results reflect that of the patient tested and are available at an additional charge. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Specimen Type: Saliva
Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.
Supplies: Saliva Swab Collection Kit (T786)
Specimen Volume: 1 Swab
Collection Instructions: Collect and send specimen per kit instructions.
Specimen Stability Information: Ambient (preferred) 30 days/Refrigerated 30 days
Additional information: Saliva specimens are acceptable but not recommended. Due to lower quantity/quality of DNA yielded from saliva, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.
Specimen Type: Skin biopsy
Supplies: Fibroblast Biopsy Transport Media (T115)
Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin.
Specimen Volume: 4-mm Punch
Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours
Additional Information:
1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks are required to culture fibroblasts before genetic testing can occur.
Specimen Type: Cultured fibroblasts
Source: Skin
Container/Tube: T-25 flask
Specimen Volume: 2 Flasks
Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy.
Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours
Additional Information:
1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks are required to culture fibroblasts before genetic testing can occur.
Specimen Type: Tissue biopsy
Supplies: Hank's Solution (T132)
Container/Tube: Sterile container with sterile Hank's balanced salt solution, Ringer's solution, or normal saline
Specimen Volume: 0.5 to 3 cm(3) or larger
Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours
Additional Information:
1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks are required to culture fibroblasts before genetic testing can occur.
Specimen Type: Blood spot
Supplies: Card-Blood Spot Collection (Filter Paper) (T493)
Container/Tube:
Preferred: Collection card (Whatman Protein Saver 903 Paper)
Acceptable: PerkinElmer 226 filter paper or blood spot collection card
Specimen Volume: 2 to 5 Blood spots
Collection Instructions:
1. An alternative blood collection option for a patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect a Dried Blood Spot Sample.
2. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.
3. Do not expose specimen to heat or direct sunlight.
4. Do not stack wet specimens.
5. Keep specimen dry.
Send: Ambient (preferred)/Refrigerated
Additional Information:
1. Blood spot specimens are acceptable but not recommended. Multiple extractions will be required to obtain sufficient yield for supplemental analysis, and there is significant risk for test failure due to insufficient DNA.
2. Due to lower concentration of DNA yielded from blood spot, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.
3. For collection instructions, see Blood Spot Collection Instructions
4. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777)
5. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800)
Specimen Type: Extracted DNA
Container/Tube:
Preferred: Screw Cap Micro Tube, 2 mL with skirted conical base
Acceptable: Matrix tube, 1 mL
Collection Instructions:
1. The preferred volume is at least 100 mcL at a concentration of 75 ng/mcL.
2. Include concentration and volume on tube.
Specimen Stability: Frozen (preferred) 1 year/Ambient/Refrigerated
Additional Information: DNA must be extracted in a CLIA-certified laboratory or equivalent and must be extracted from a specimen type listed as acceptable for this test (including applicable anticoagulants). Our laboratory has experience with Chemagic, Puregene, Autopure, MagnaPure, and EZ1 extraction platforms and cannot guarantee that all extraction methods are compatible with this test. If testing fails, one repeat will be attempted, and if unsuccessful, the test will be reported as failed, and a charge will be applied. If applicable, specific gene regions that were unable to be interrogated due to DNA quality will be noted in the report.
PRENATAL SPECIMENS
Due to its complexity, consultation with the laboratory is required for all prenatal testing; call 800-533-1710 to speak to a genetic counselor.
Specimen Type: Amniotic fluid
Container/Tube: Amniotic fluid container
Specimen Volume: 20 mL
Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours
Additional Information: Specimen will only be tested after culture.
1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
2. A separate culture charge will be assessed under CULAF / Culture for Genetic Testing, Amniotic Fluid. An additional 2 to 3 weeks are required to culture amniotic fluid before genetic testing can occur.
3. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Specimen Type: Prenatal cultured fibroblasts (eg, products of conception), amniocytes, or other confluent cultured cells. This does not include cultured chorionic villi.
Container/Tube: T-25 flask
Specimen Volume: 2 Flasks
Collection Instructions: Submit confluent cultured cells from another laboratory.
Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours
Additional Information:
1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing.
3. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Specimen Type: Chorionic villi
Container/Tube: 15-mL tube containing 15 mL of transport media
Specimen Volume: 20 mg
Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours
Additional Information: Specimen can only tested after culture.
1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks are required to culture fibroblasts before genetic testing can occur.
3. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Specimen Type: Cultured chorionic villi
Container/Tube: T-25 flasks
Specimen Volume: 2 full flasks
Collection Instructions: Submit confluent cultured cells from another laboratory.
Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours
Additional Information:
1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing.
3. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Forms
1. New York Clients-Informed consent is required.
Document on the request form or electronic order that a copy is on file. The following documents are available:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing (Spanish) (T826)
2. Molecular Genetics: Biochemical Disorders Patient Information(T527)
3. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
Useful For
Confirmation of diagnosis of Pompe disease as a follow-up to biochemical analyses
Genetics Test Information
This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in the GAA gene associated with Pompe disease. See Method Description for additional details.
Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, recurrence risk assessment, familial screening, and genetic counseling for Pompe disease.
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| CULFB | Fibroblast Culture for Genetic Test | Yes | No |
| CULAF | Amniotic Fluid Culture/Genetic Test | Yes | No |
| MATCC | Maternal Cell Contamination, B | Yes | No |
Testing Algorithm
Prenatal specimens:
If an amniotic fluid specimen or cultured amniocytes are received, an amniotic fluid culture will be performed at an additional charge.
If a chorionic villi specimen or cultured chorionic villi are received, a fibroblast culture will be performed at an additional charge.
For any prenatal specimen that is received, maternal cell contamination testing will be performed at an additional charge.
Skin biopsy or cultured fibroblast specimens:
For skin biopsy or cultured fibroblast specimens, a fibroblast culture will be performed at an additional charge. If viable cells are not obtained, the client will be notified.
Method Name
Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing
Reporting Name
GAA Gene AnalysisSpecimen Type
VariesSpecimen Minimum Volume
See Specimen Required
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Varies | Varies | |
Clinical Information
Note: Where applicable, verbiage refers to sex assigned at birth.
Pompe disease, also known as glycogen storage disease type II, is an autosomal recessive condition caused by deficiency of acid alpha-glucosidase, encoded by the GAA gene. Enzyme insufficiency results in heterogenous symptoms including muscle weakness, cardiomyopathy, and respiratory problems. The diagnosis of this condition relies on both clinical and laboratory evaluation. Clinically, Pompe disease is categorized into infantile-onset and late-onset forms based on age-of-onset, organ involvement, and rate of progression. The infantile-onset form (or classic Pompe disease) is the most severe presentation and is characterized by early-onset (before 12 months of age) and rapid progression of cardiac, liver, and muscle problems resulting in death within the first year unless treated. The late-onset form includes individuals presenting with proximal muscle weakness and respiratory insufficiency without clinically significant cardiomyopathy at any age. The rate of progression and severity of symptoms is quite variable, particularly in the late-onset forms. The incidence varies by clinical type and ethnic population; the combined incidence is approximately 1 in 40,000 individuals.
Measurement of acid alpha-glucosidase activity can be ordered on blood via test, GAAW / Acid Alpha-Glucosidase, Leukocytes. However, the calculated ratio of creatine and creatinine to acid-alpha glucosidase activity is also useful for identifying patients with a suspected diagnosis of Pompe disease. This ratio is accessible in dried blood spot specimens. For patients older than 6 weeks, order PDBS / Pompe Disease, Blood Spot; for patients 6 weeks and younger, order PD2T / Pompe Disease Second-Tier Newborn Screening, Blood Spot. Additionally, measurement of urine glucotetrasaccharide biomarkers can aid in the diagnosis and ongoing therapeutic monitoring via test HEX4 / Glucotetrasaccharides, Random, Urine. When clinical manifestations and laboratory testing are supportive of a diagnosis of Pompe disease, variant analysis of the GAA gene is warranted.
Over 250 different variants have been identified in this gene including point alterations and large deletions. Identification of genetic variants provides confirmation of the diagnosis and allows for subsequent testing of at-risk family members.
Reference Values
An interpretive report will be provided.
Interpretation
All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Clinical Reference
1. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424
2. Kishnani PS, Steiner RD, Bali D, et al. Pompe disease diagnosis and management guideline. Genet Med. 2006;8(5):267-288
3. Van der Ploeg AT, Reuser AJJ. Pompe's disease. Lancet. 2008;372(9646):1342-1353
4. Kroos M, Pomponio RJ, van Vliet L, et al. Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating. Hum Mut. 2008;29(6):E13-26
5. Reuser AJJ, Hirschhorn R, Kroos MA. Pompe disease: Glycogen storage disease type II, acid a-glucosidase (acid maltase) deficiency. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. eds. Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed March 21, 2025. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709§ionid=225890450
6. Goldstein J, McGalughon J, Kanavy D, et al. Variant classification for Pompe disease; ACMG/AMP specifications from the ClinGen Lysosomal Disease Variant Curation Expert Panel. Mol Genet Metab. 2023;140(1-2):107715
Day(s) Performed
Varies
Report Available
10 to 14 daysTest Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81406
88233-Tissue culture, skin or solid tissue biopsy (if appropriate)
88240-Cryopreservation (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| GAAN | GAA Gene Analysis | 76034-8 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 622583 | Test Description | 62364-5 |
| 622584 | Specimen | 31208-2 |
| 622585 | Source | 31208-2 |
| 622586 | Result Summary | 50397-9 |
| 622587 | Result | 82939-0 |
| 622588 | Interpretation | 69047-9 |
| 622589 | Additional Results | 82939-0 |
| 622590 | Resources | 99622-3 |
| 622591 | Additional Information | 48767-8 |
| 622592 | Method | 85069-3 |
| 622593 | Genes Analyzed | 48018-6 |
| 622594 | Disclaimer | 62364-5 |
| 622595 | Released By | 18771-6 |
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