Interpretive Handbook

Test 89897 :
Pompe Disease, Known Mutation

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 condition caused by deficiency of acid alpha-glucosidase. Enzyme insufficiency results in symptoms such as muscle weakness, cardiomyopathy, and respiratory problems. Mutations in the GAA gene (which encodes acid alpha-glucosidase) are associated with Pompe disease.


The diagnosis of this heterogeneous condition relies on both clinical and laboratory evaluation. Clinically, the condition is categorized into infantile and late-onset forms based on age of onset, organ involvement, and rate of progression. The infantile form (or classic Pompe disease) is the most severe form and is characterized by early onset and rapid progression of cardiac, liver, and muscle problems resulting in death within the first year. The infantile variant form has a similar age of onset but a milder clinical presentation. On the less severe end of the spectrum is the late-onset form with childhood, juvenile or adult onset. 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.


Biochemical testing of acid alpha-glucosidase in blood spot specimens is useful for individuals with a suspected diagnosis of Pompe disease (GAABS / Acid Alpha-Glucosidase, Blood Spot). When clinical manifestations and results of that analysis are supportive of a diagnosis of Pompe disease, mutation analysis of the GAA gene is warranted.


Over 250 different mutations have been identified in this gene including point mutations and large deletions. This test performs sequence analysis for known familial mutation(s) for at risk family members, either for identification of carriers or diagnostic purposes.

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

Confirmation of diagnosis of Pompe disease (as a follow up to biochemical analyses) for individuals from families in which a known familial mutation(s) has been previously identified


Carrier screening for individuals at risk for known familial mutation(s) in the GAA gene

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

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

The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order GAAMS / Pompe Disease, Full Gene Sequencing.


Analysis is performed for the familial mutation(s) provided only. This assay does not rule out the presence of other mutations within this gene that may be associated with Pompe disease.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.


A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.

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.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Kishnani PS, Steiner RD, et al: Pompe disease diagnosis and management guideline. Genet Med 2006;8(5):267-288

2. Van der Ploeg AT, Reuser AJJ: Pompe's disease. Lancet 2008;372(9646):1342-1353

3. Kroos M, Pomponio RJ, 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

4. Hirschhorn R, Reuser AJJ: Glycogen storage disease type II: (acid maltase) deficiency. In The Metabolic and Molecular Bases of Inherited Disease (OMMBID). Edited by CR Scriver, AL Beaudet, WS Sly, et al: McGraw-Hill, New York, chapter 135. Available at, Accessed 3-6-08