Targeted gene panel screening is an effective tool to identify undiagnosed late onset Pompe disease

Marco Savarese, Annalaura Torella, Olimpia Musumeci, Corrado Angelini, Guja Astrea, Luca Bello, Claudio Bruno, Giacomo Pietro Comi, Giuseppina Di Fruscio, Giulio Piluso, Giuseppe Di Iorio, Manuela Ergoli, Gaia Esposito, Marina Fanin, Olimpia Farina, Chiara Fiorillo, Arcomaria Garofalo, Teresa Giugliano, Francesca Magri, Carlo MinettiMaurizio Moggio, Luigia Passamano, Elena Pegoraro, Ester Picillo, Simone Sampaolo, Filippo Maria Santorelli, Claudio Semplicini, Bjarne Udd, Antonio Toscano, Luisa Politano, Vincenzo Nigro

Research output: Contribution to journalArticlepeer-review


Mutations in the GAA gene may cause a late onset Pompe disease presenting with proximal weakness without the characteristic muscle pathology, and therefore a test for GAA activity is the first tier analysis in all undiagnosed patients with hyperCKemia and/or limb-girdle muscular weakness. By using MotorPlex, a targeted gene panel for next generation sequencing, we analyzed GAA and other muscle disease-genes in a large cohort of undiagnosed patients with suspected inherited skeletal muscle disorders (n = 504). In this cohort, 275 patients presented with limb-girdle phenotype and/or an isolated hyperCKemia. Mutational analysis identified GAA mutations in ten patients. Further seven affected relatives were identified by segregation studies. All the patients carried the common GAA mutation c.-32-13T >G and a second, previously reported mutation. In the subcohort of 275 patients with proximal muscle weakness and/or hyperCKemia, we identified late-onset Pompe disease in 10 patients. The clinical overlap between Pompe disease and LGMDs or other skeletal muscle disorders suggests that GAA and the genes causing a metabolic myopathy should be analyzed in all the gene panels used for testing neuromuscular patients. However, enzymatic tests are essential for the interpretation and validation of genetic results.

Original languageEnglish
Pages (from-to)586-591
JournalNeuromuscular Disorders
Issue number7
Publication statusPublished - 2018


  • GAA
  • Gene panels
  • HyperCKemia
  • Late onset Pompe disease (LOPD)
  • LGMD
  • Metabolic myopathies

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)


Dive into the research topics of 'Targeted gene panel screening is an effective tool to identify undiagnosed late onset Pompe disease'. Together they form a unique fingerprint.

Cite this