Test Catalog

Test ID: PDBS    
Pompe Disease, Blood Spot

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

Evaluation of patients with a clinical presentation suggestive of Pompe disease (muscle hypotonia, weakness, or cardiomyopathy) outside of the newborn screening setting

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

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

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 mutations 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, eventually, organ dysfunction. This leads to progressive muscle weakness, cardiomyopathy, and, eventually, death. Patients 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. Delayed diagnosis of symptomatic patients with later onset Pompe disease is not unusual due to nonspecific and overlapping presentation (such as proximal muscle weakness and respiratory insufficiency) with more common neuromuscular diseases.


The clinical phenotype of Pompe disease lies on a spectrum, with differing clinical phenotypes 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 prompt diagnosis of Pompe disease desirable, as early initiation of treatment may improve prognosis.


The ratio calculated between the creatine (Cre):creatinine (Crn) ratio as the numerator and the activity of GAA as the denominator can differentiate true cases of infantile and late-onset Pompe disease from false-positive cases such as carriers and pseudodeficiency of GAA enzyme. This determination 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).

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.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

An interpretive report (including acid alpha-glucosidase (GAA) activity and [Creatine/Creatinine]/GAA ratio, if applicable) is provided.


The quantitative measurements of informative metabolites and related ratios are evaluated using the Collaborative Laboratory Integrated Reports (CLIR) system. The report is in text form only, indicating if the applicable ratio is normal or abnormal and whether or not the CLIR postanalytical tool is informative for Pompe disease. Abnormal results are not sufficient to conclusively establish a diagnosis of a particular disease. To verify a preliminary diagnosis, independent biochemical (ie, in vitro enzyme assay) or molecular genetic analyses are required, many of which are offered within Mayo Clinic's Division of Laboratory Genetics and Genomics. Recommendations for additional biochemical testing and confirmatory studies (enzyme assay, biomarker testing, molecular analysis) are provided in the interpretative report.

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

For asymptomatic individuals, this test may not detect some late-onset and variant forms of Pompe disease.


Carrier status (heterozygosity) for Pompe disease cannot be reliably detected.


A positive test result is strongly suggestive of a diagnosis but requires follow-up molecular genetic analysis of the GAA gene, which is best coordinated by local genetics providers.

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

1. Pascual JM, Roe CR: Systemic Metabolic Abnormalities in Adult-onset Acid Maltase Deficiency. JAMA Neurol 2013;70(6):756-763

2. Tortorelli S, Eckerman JS, Orsini JJ, et al: Moonlighting newborn screening markers: The incidental discovery of a second tier test for Pompe disease Genet Med Epub ahead of print: 2017 Nov 2. doi: 10.1038/gim.2017.190

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