TY - JOUR
T1 - Late-onset Pompe disease is prevalent in unclassified limb-girdle muscular dystrophies
AU - Preisler, Nicolai
AU - Lukacs, Zoltan
AU - Vinge, Lotte
AU - Madsen, Karen Lindhardt
AU - Husu, Edith
AU - Hansen, Regitze Sølling
AU - Duno, Morten
AU - Andersen, Henning
AU - Laub, Michael Søren Haae
AU - Vissing, John
PY - 2013/11
Y1 - 2013/11
N2 - 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.
AB - 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.
U2 - 10.1016/j.ymgme.2013.08.005
DO - 10.1016/j.ymgme.2013.08.005
M3 - Journal article
C2 - 24011652
SN - 1096-7192
VL - 110
SP - 287
EP - 289
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 3
ER -