Toward deconstructing the phenotype of late-onset Pompe disease


  • Angela Schüller,

  • Stephan Wenninger,

  • Nicola Strigl-Pill,

  • Benedikt Schoser

    Corresponding author
    • Friedrich-Baur-Institute, Department of Neurology Ludwig-Maximilians-University, Munich Ziemssenstr. 1a D-80336 Munich, Germany.
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    • Benedikt Schoser is senior consultant at the Friedrich-Baur-Institute, Dept. of Neurology at the Ludwig-Maximilians-University of Munich, Germany. He is coordinator of the diagnostic working group within the German MD-NET, member of the German reference group for neuromuscular disorders, and TREAT-NMD. Benedikt Schoser has a long-standing interest in the pathogenesis of muscular dystrophies, myotonic dystrophies, and metabolic myopathies. He is engaged in all types of morphological and molecular analyses including animal models and human myoblast cell culture studies. He has a special interest in translational therapy of myotonic dystrophies and glycogen storage disorders.

  • Doctors Angela Schüller, Stephan Wenninger, and Nicola Strigl-Pill are members of Dr. Schoseŕs working group at the Friedrich-Baur-Institute.

  • How to cite this article: Schüller A, Wenninger S, Strigl-Pill N, Schoser B. 2012. Toward deconstructing the phenotype of late-onset Pompe disease. Am J Med Genet Part C Semin Med Genet 160C:80–88.


Pompe disease (glycogen storage disease type 2 or acid maltase deficiency) is a rare autosomal recessive lysosomal storage disorder. Since the advent of ERT a lot has been learned about the phenotypic spectrum especially in the late onset patients. We describe in detail 44 patients diagnosed with late-onset Pompe disease (LOPD) at our neuromuscular department from 1985 to 2011 and compare them to patients with LOPD in the literature of the past 40 years. Study of the Munich LOPD group revealed varying musculoskeletal and cardio-cerebrovascular manifestation patterns. Several of these symptom patterns commonly appeared in conjunction with one another, highlighting the multisystem involvement of this condition. Common symptom patterns include: (i) Classic limb girdle and diaphragmatic weakness, (ii) rigid spine syndrome (RSS), scoliosis, and low body mass, and (iii) several cardio-cerebrovascular manifestation patterns. The most common presentation, limb girdle and diaphragmatic weakness, appeared in 78% (34/44) of our patients and over 80% of those in the literature. Sixteen percent (7/44) of our patients presented with rigid spine, scoliosis, and low body mass. Although scoliosis had a reported frequency of 33% in the general LOPD patient population, the literature only occasionally reported low body mass and RSS. Importantly, a multisystem extramuscular finding accompanied by cardio-cerebrovascular manifestations was found in 29% (13/44) of our LOPD patients; the literature showed an increasing prevalence of this latter finding. By examining the phenotype of patients with confirmed LOPD, we found a more subtle clinical multisystem involvement in LOPD. Whether patients presenting with the different symptom patterns respond differently to enzyme replacement therapy remains a key question for future research. © 2012 Wiley Periodicals, Inc.