Late-onset Pompe disease is prevalent in unclassified limb-girdle muscular dystrophies

Mol Genet Metab. 2013 Nov;110(3):287-9. doi: 10.1016/j.ymgme.2013.08.005. Epub 2013 Aug 15.


Objective: Late-onset Pompe disease is a rare, but potentially treatable metabolic myopathy, and therefore should not be overlooked. However, it is not unusual that patients go undiagnosed for many years. We hypothesized that patients with late-onset Pompe disease may have been overlooked in a population of patients with unclassified neuromuscular disease.

Methods: We used DBS (dried blood spots) to screen for Pompe disease in the two largest neuromuscular clinics and one of the main respiratory centers in Denmark. We selected patients with unclassified LGDM (limb-girdle muscular dystrophy), idiopathic elevation of creatine kinase, unexplained myopathy on muscle biopsy, unexplained restrictive respiratory insufficiency or unspecified myopathy for screening.

Results: 177 patients were found eligible for inclusion, and 103 (58.2%) patients accepted screening. Three patients with Pompe disease were identified with DBS, and subsequent genetic testing revealed known pathogenic mutations in the GAA gene. All three patients were found among 38 patients with unclassified LGMD (8%).

Conclusion: Our findings indicate that a DBS should be considered early in the diagnostic work-up of patients with an LGMD phenotype, to rule out Pompe disease. Retrospectively, all 3 patients presented with "red flags" more compatible with Pompe disease than LGMD, including; 1) mild non-dystrophic, myopathic features on muscle biopsy, 2) creatine kinase levels below 1000, and 3) disproportionate axial and respiratory muscle involvement in comparison with limb muscle involvement.

Keywords: CK; DBS; Dried blood spots; GAA; Glycogen storage disease; LGMD; Late-onset Pompe disease; Limb-girdle muscular dystrophy phenotype; Screening; acid alpha-glucosidase; creatine kinase; dried blood spots; limb-girdle muscular dystrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Creatine Kinase / blood
  • Delayed Diagnosis
  • Denmark
  • Female
  • Glycogen Storage Disease Type II / complications*
  • Glycogen Storage Disease Type II / diagnosis*
  • Glycogen Storage Disease Type II / genetics
  • Humans
  • Male
  • Middle Aged
  • Muscular Dystrophies, Limb-Girdle / complications*
  • Muscular Dystrophies, Limb-Girdle / diagnosis
  • Mutation
  • Phenotype
  • Retrospective Studies
  • Young Adult
  • alpha-Glucosidases / genetics
  • alpha-Glucosidases / metabolism


  • Creatine Kinase
  • GAA protein, human
  • alpha-Glucosidases