Interpretive Handbook

Test 89898 :
Pompe Disease, Full Gene Sequencing

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 or fibroblasts 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. GAA full gene sequencing provided by this test will detect 2 mutations in approximately 83% to 93% of individuals with confirmed GAA enzyme deficiency. Identification of mutations provides confirmation of the diagnosis and allows for subsequent testing of at risk family members.

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)

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

A small percentage of individuals who are carriers or have a diagnosis of Pompe disease may have a mutation that is not identified by this method (eg, large genomic deletions or duplications, promoter mutations). The absence of a mutation(s), therefore, does not eliminate the possibility of positive carrier status or the diagnosis of Pompe disease. For carrier testing, it is important to first document the presence of a GAA gene mutation in an affected family member.


In some cases, DNA alterations of undetermined significance may be identified.


Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.


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.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

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, Bali D, et al: Pompe disease diagnosis and management guideline. Genet Med 2006 May;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, 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

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