Test Catalog

Test ID: GAAW    
Acid Alpha-Glucosidase, Leukocytes

Useful For Suggests clinical disorders or settings where the test may be helpful

Diagnosis of Pompe disease

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test provides diagnostic testing for individuals with decreased alpha-glucosidase activity on newborn screen or clinical signs and symptoms suspicious for Pompe disease.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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 acid alpha-glucosidase (GAA; acid maltase) due to variants 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 physiologic cell turnover accumulates, causing lysosomal swelling, cell damage, and organ dysfunction. This leads to progressive muscle weakness, cardiomyopathy, and, eventually, death. Individuals with Pompe disease, especially those with infantile, childhood, and juvenile onset, can have elevations of serum enzymes (such as creatine kinase) secondary to cellular dysfunction.


The clinical phenotype of Pompe disease lies on a spectrum dependent on age of onset and residual enzyme activity. Complete loss of enzyme activity causes onset in infancy leading to death, typically within the first year of life when left untreated. Juvenile and adult-onset forms, as the names suggest, are characterized by later onset and longer survival. All disease variants are eventually associated with progressive muscle weakness and respiratory insufficiency. Cardiomyopathy is associated almost exclusively with the infantile form. Treatment with enzyme replacement therapy is available, making early diagnosis of Pompe disease desirable, as early initiation of treatment may improve prognosis. Newborn screening can identify individuals with all forms of Pompe disease, even before onset of symptoms. Unaffected individuals with GAA pseudodeficiency alleles and carriers may also be identified by newborn screening.


Determination of GAA enzyme activity in leukocytes can be helpful in distinguishing between infantile and later onset Pompe disease, but it may also be deficient in individuals with pseudodeficiency alleles and in some carriers. Urine glucotetrasaccharides (HEX4 / Glucotetrasaccharides, Random, Urine) have been shown to be elevated in some individuals, particularly those with infantile onset, and may aid in initial diagnosis and for treatment monitoring.


Molecular genetic analysis of the GAA gene (GAAZ / Pompe Disease, Full Gene Analysis, Varies) is necessary for differentiating alterations from disease-causing variants in affected individuals and for carrier detection in family members.

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.

> or =1.50 nmol/hour/mg protein

An interpretive report is provided.

Interpretation Provides information to assist in interpretation of the test results

When abnormal results are detected, a detailed interpretation is given, including an overview of the results and of their significance, a correlation to available clinical information, elements of differential diagnosis, recommendations for additional biochemical testing and in vitro, confirmatory studies (enzyme assay, molecular analysis), and a phone number to reach one of the laboratory directors in case the referring physician has additional questions.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Pseudodeficiency results in low measured acid alpha-glucosidase (GAA) activity, but it is not consistent with Pompe disease. Molecular analysis (GAAZ / Pompe Disease, Full Gene Analysis, Varies) should be performed to resolve the clinical question.


Additional biochemical or molecular testing is recommended to confirm a diagnosis if an enzyme deficiency is detected by this screening test.


Enzyme levels may be normal in individuals receiving enzyme replacement therapy.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Elliott S, Buroker N, Cournoyer JJ, et al: Pilot study of newborn screening for six lysosomal storage diseases using tandem mass spectrometry. Mol Genet Metab. 2016 Aug;118(4):304-309

2. Matern D, Gavrilov D, Oglesbee D, et al: Newborn screening for lysosomal storage disorders. Semin Perinatol. 2015 Apr;39(3):206-216

3. 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 June 30, 2020. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225890450

4. Lin N, Huang J, Violante S, et al: Liquid chromatography-tandem mass spectrometry assay of leukocyte acid alpha-glucosidase for post-newborn screening evaluation of Pompe disease. Clin Chem. 2017 Apr;63(4):842-851

5. Leslie N, Bailey L: Pompe disease. In: Adam MP, Ardinger HH, Pagon RA, et al. GeneReviews [Internet]. University of Washington, Seattle; 2007. Updated May 2017. Accessed February 11, 2019. Available at: www.ncbi.nlm.nih.gov/books/NBK1261/

Special Instructions Library of PDFs including pertinent information and forms related to the test