... / ... / ... / ... / Pompe Center / Diagnosis


Presenting symptoms
Classic infantile Pompe disease typically presents within the first several months of life.  Affected infants have profound and progressive muscle weakness manifested in a 'floppy baby' appearance. Other key manifestations include respiratory insufficiency, marked cardiomegaly, failure to reach developmental milestones, feeding difficulties and hepatomegaly.

There also are milder forms of Pompe disease presenting later in life with progressive weakness of mainly the skeletal muscles of the trunk and the lower limbs. Patients often have a waddling gait and may have difficulty taking stairs or rising from a chair. Common respiratory symptoms include shortness of breath, sleep-disordered breathing, and progression to respiratory failure. Other symptoms may include scoliosis, scapular winging, muscle pain, fatigue and frequent falls.

When Pompe disease is suspected, the diagnosis can be confirmed by demonstrating the lack of acid α-glucosidase activity in cells or tissues of the patient. The acid α-glucosidase deficiency in Pompe disease is caused by pathogenic mutations in the gene (DNA) prescribing the mode of synthesis and function of acid α-glucosidase. If the mutations are known, Pompe disease can also be diagnosed by DNA analysis.

Enzymatic diagnosis
Cultured skin fibroblasts, muscle tissue and leukocytes are routinely used for the enzymatic diagnosis of Pompe disease. In some cases, more than one tissue source needs to be analysed to confirm the diagnosis. The use of skin fibroblasts offers high sensitivity and specificity and has the additional advantage that fibroblasts can be amplified in culture and stored in liquid nitrogen so that they last forever. A muscle biopsy provides the opportunity to visually inspect the muscle tissue and judge the severity of muscle damage, but the small tissue specimen is not always representative for the total muscle quality. Leucocytes are easy to collect, but the analysis of acid α-glucosidase activity is complicated by the presence of contaminating α-glucosidases.

DNA analysis
DNA analysis is often performed, once the acid α-glucosidase deficiency has been established. DNA analysis is mandatory to identify unaffected carriers and pre-symptomatic patients in an affected family. Enzymatic diagnosis is not suitable for this purpose.

Prenatal diagnosis
Chorionic villi (primitive placenta) and amniocytes (free floating cells of the fetus) are used as starting material for both enzyme activity based as well as DNA based prenatal diagnosis. But, the familial mutations have to be known in advance to guarantee the informative outcome of DNA analysis. Enzyme activity based prenatal diagnosis of classic infantile Pompe disease is very reliable, but cumbersome in families with milder forms of disease due to residual acid α-glucosidase activity. DNA diagnosis is preferred in the latter situations.

Diagnostic services provided by Erasmus MC
Erasmus MC provides services and consultancy with regard to diagnostic questions and requests from health care professionals. Please contact us for further information.




All rights reserved. No part of this text may be reproduced without prior written permission of the Pompe Center.