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Glycogen Storage Disease Type II (Pompe Disease) via the GAA Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
GAA 81406 81406,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9605GAA81406 81406,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Maxime Cadieux-Dion, PhD

Clinical Features and Genetics

Clinical Features

Glycogen Storage Disease Type II (GSDII, also known as Pompe Disease or acid maltase deficiency) is caused by defects in the lysosomal degradation of glycogen. Symptoms consist primarily of weakness in muscles, including cardiac and respiratory muscles. Pompe disease has a broad clinical spectrum with variable age of onset, severity of symptoms, and rate of disease progression. Phenotypes range from a rapidly progressive infantile form to a slowly progressive late-onset form (Leslie and Tinkle 2013; Chen et al. 2014; Adeva-Andany et al. 2016). The classic infantile form of Pompe Disease is the most severe and is usually fatal. Affected infants present with profound hypotonia, muscle weakness, hyporeflexia, enlarged tongue, and hypertrophic cardiomyopathy. Diagnosis may be based on typical EKG findings which include large QRS complexes and shortened PR intervals (Kishnani et al. 2006). In the juvenile form of the disease, affected children have hypotonia and weakness of limb girdle and truncal muscles, but there is no overt cardiac disease. Adult-onset Pompe Disease has a long latency and affected individuals may live to old age. Decreased muscle strength and weakness develop, most commonly in the third or fourth decade, but cardiac involvement, if any, is minimal (Leslie and Tinkle 2013; Chen et al. 2014; Adeva-Andany et al. 2016). It should be noted that enzyme replacement therapy (ERT) with alglucosidase alfa is a treatment option that is commercially available for all forms of Pompe Disease (van der Ploeg and Reuser 2008; Leslie and Tinkle 2013; Doerfler et al. 2016).


Glycogen Storage Disease Type II is caused by a deficiency of α-1,4-glucosidase, an enzyme required for the degradation of lysosomal glycogen (Hers 1963). The disorder is inherited in an autosomal recessive manner, and the estimated disease incidence is approximately 1 in 40,000 to 1 in 50,000. Pathogenic variants within the GAA gene encoding the acid alpha-glucosidase enzyme are the only known cause of the disease, and over 400 different GAA pathogenic variants have been reported (Erasmus MC. Pompe Center; Human Gene Mutation Database). The pathogenic variants are distributed throughout the length of the gene. Missense and nonsense pathogenic variants predominate, although splicing and regulatory variants as well as small and gross deletions and insertions have all been reported. Some correlations have been made between specific pathogenic variants and disease severity (Hermans et al. 2004; Wan et al. 2008; Kroos et al. 2012). One common pathogenic variant in intron 1 of the GAA gene, defined as c.-32-13T>G, has been found in almost two-thirds of patients with adult onset disease (Huie et al. 1994). Pompe Disease can be found in ethnically diverse populations, including European Whites, Hispanics, and Asians. Although founder mutations are known in some genetically isolated populations, in the overall American population no pathogenic variants are predominant.

Clinical Sensitivity - Sequencing with CNV PGxome

Through gene sequencing, Hermans et al. (2004) were able to detect at least one likely causative variant in every one of the 29 GSDII patients in their cohort. Two likely causative variants were identified in 24 out of the 29 patients. Similarly, in a study of late-onset GSD Type II patients, Montalvo et al. (2006) detected at least one likely causative variant in all 40 patients studied, and two variants in 37 of the patients. Liu et al. (2014) studied late-onset GSD Type II patients in a Chinese population and found at least one likely causative variant in all 27 patients studied and two likely causative variants in 25 of the 27 patients. Overall, this suggests a clinical sensitivity of ~95% for this test.

While most GAA pathogenic variants will be picked up by gene sequencing, at least 8 different gross deletions have been reported (Leslie and Tinkle 2013). One relatively common pathogenic variant, seen in approximately 5% to 7% of causative alleles, involves the deletion of exon 18 (Van der Kraan et al. 1994). Please see the methods tab for limitations on CNV detection.

Testing Strategy

This test provides full coverage of all coding exons of the GAA gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

The c.-32-13T>G pathogenic variant that is sometimes found in patients with late-onset disease is covered.

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Candidates for this test are patients with clinical symptoms, biochemical test results and/or enzyme assay results consistent with GSD Type II, including infants with a positive newborn screen. Testing is also indicated for family members of patients with known GAA variants. We will also sequence the GAA gene to determine carrier status.


Official Gene Symbol OMIM ID
GAA 606800
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Glycogen Storage Disease Type II AR 232300

Related Tests

Comprehensive Cardiology Panel
Glycogen Storage Disease Type II (Pompe Disease) via the GAA Gene, Exon 18 Deletion


  • Adeva-Andany MM et al. 2016. Bba Clinical. 5: 85-100. PubMed ID: 27051594
  • Chen Y., Kishnani P.S. and Koeberl D. 2014. Glycogen Storage Diseases. In: Valle D, Beaudet AL, Vogelstein B, et al., editors. New York, NY: McGraw-Hill. OMMBID.
  • Doerfler P.A. et al. 2016. Molecular Therapy. Methods & Clinical Development. 3: 15053. PubMed ID: 26858964
  • Erasmus MC. Pompe Center (http://www.erasmusmc.nl/klinische_genetica/research/lijnen/pompe_center/?lang=en)
  • Hermans M.M. et al. 2004. Human Mutation. 23: 47-56. PubMed ID: 14695532
  • Hers H.G. 1963. The Biochemical Journal. 86: 11-6. PubMed ID: 13954110
  • Huie M.L. et al. 1994. Human Molecular Genetics. 3: 2231-6. PubMed ID: 7881425
  • Human Gene Mutation Database (Bio-base).
  • Kishnani Priya S et al. 2006. Genetics in Medicine. 8: 267-288. PubMed ID: 16702877
  • Kroos M. et al. 2012. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics. 160C: 59-68. PubMed ID: 22253258
  • Leslie N. and Tinkle B.T. 2013. Glycogen Storage Disease Type II (Pompe Disease). In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301438
  • Liu X. et al. 2014. Bmc Medical Genetics. 15: 141. PubMed ID: 25526786
  • Montalvo A.L. et al. 2006. Human Mutation. 27: 999-1006. PubMed ID: 16917947
  • Van der Kraan M. et al. 1994. Biochemical and Biophysical Research Communications. 203: 1535-41. PubMed ID: 7945303
  • van der Ploeg A.T., Reuser AJ. 2008. Lancet. 372: 1342-53. PubMed ID: 18929906
  • Wan L. et al. 2008. Journal of Neurology. 255: 831-8. PubMed ID: 18458862


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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