We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Review |

Diagnosis of Pompe Disease Muscle Biopsy vs Blood-Based Assays

John Vissing, MD, DMSci1; Zoltan Lukacs, PhD2; Volker Straub, MD, PhD3
[+] Author Affiliations
1Neuromuscular Research Unit, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
2Department of Pediatrics and Institute of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
3Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, England
JAMA Neurol. 2013;70(7):923-927. doi:10.1001/2013.jamaneurol.486.
Text Size: A A A
Published online

The diagnosis of Pompe disease (acid maltase deficiency, glycogen storage disease type II) in children and adults can be challenging because of the heterogeneous clinical presentation and considerable overlap of signs and symptoms found in other neuromuscular diseases. This review evaluates some of the methods used in the diagnosis and differential diagnosis of late-onset Pompe disease. Muscle biopsy is commonly used as an early diagnostic tool in the evaluation of muscle disease. However, experience has shown that relying solely on visualizing a periodic acid–Schiff–positive vacuolar myopathy to identify late-onset Pompe disease often leads to false-negative results and subsequent delays in identification and treatment of the disorder. Serum creatine kinase level can be normal or only mildly elevated in late-onset Pompe disease and is not very helpful alone to suggest the diagnosis, but in combination with proximal and axial weakness it may raise the suspicion for Pompe disease. A simple blood-based assay to measure the level of α-glucosidase activity is the optimal initial test for confirming or excluding Pompe disease. A timely and accurate diagnosis of late-onset Pompe disease likely will improve patient outcomes as care standards including enzyme replacement therapy can be applied and complications can be anticipated. Increased awareness of the clinical phenotype of Pompe disease is therefore warranted to expedite diagnostic screening for this condition with blood-based enzymatic assays.

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?


Place holder to copy figure label and caption
Figure 1.
Hematoxylin-eosin Staining of Muscle Biopsy Tissue From Patients With Confirmed Pompe Disease

A and B, Unspecific myopathic changes with relatively preserved muscle structure and no evidence of vacuolar myopathy or glycogen accumulation. C, Vacuolar myopathy (arrows) in a few muscle fibers. D, Severe vacuolar myopathy (arrow) with myofibrillar loss. (Original magnification ×10).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Dried Blood Spot Assay Specimens

A, A blood specimen spotted according to the specified guidelines, which recommend that blood be spotted from only 1 side so that the filter paper is fully soaked. The sample should be allowed to dry overnight at room temperature before being put into an envelope. B, Separation of the erythrocytes from the blood plasma, which can occur when samples are inadequately dried, for instance, when placed into plastic wrapping. When tested for α-glucosidase, moist samples may yield false-positive results that indicate normal levels of enzyme activity. C, An example of dried blood spot samples obtained with incorrect filter paper. These samples cannot be evaluated because eluting sample amounts can vary greatly. Generally, Ahlstrom 226 (Ahlstrom Filtration LLC) and Whatman 903 (Whatman/GE Healthcare Life Sciences) filter papers are acceptable and preferred for dried blood spot analyses. D, An example of overspotting, which should be avoided after an initial spot has been created. E and F, Insufficient amounts of blood. Blood spots 3 mm in diameter or smaller yield lower enzyme activity when compared with standard samples and are unsuitable for analysis.

Graphic Jump Location




Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

15 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections