Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating


  • Communicated by Elizabeth F. Neufeld

  • GAA database consortium: Hernán Amartino, Laboratorio de Neuroquímica, Buenos Aires, Argentina; Martina Baethmann, Children's Hospital ‘an der Lachnerstrasse’, Munchen, Germany; Maryam Banikazemi, Mt. Sinai School of Medicine, Manhattan, NY, USA; Nadine van der Beek, Gerard de Jong and Ans van der Ploeg, Erasmus MC, Rotterdam, The Netherlands; A Bosch, AMC, Amsterdam, The Netherlands; Barry J. Byrne, University of Florida, Gainesville, FL, USA; Joel Charrow, Children's Memorial Hospital, Chicago, IL, USA; J.P. Clancy, University of Alabama, Birmingham, AL, USA; Paula R. Clemens, University of Pittsburgh, Pittsburgh, PA, USA; Valérie Doppler and Pascal Laforêt, Institut de Myologie, Paris, France; Diana M. Escolar, Children's National Medical Center, Washington, DC, USA; Annette Feigenbaum, Hospital for Sick Children, Toronto, Ontario, Canada; Mirella Filocamo, Istituto G. Gaslini, Genova, Italy; Aly Gadalla, Galichia Heart Hospital, Wichita, KS, USA; Carl Garabedian, Sacred Heart Children's Hospital, Spokane, WA, USA; George F Gray, Birmingham Children's Hospital, Birmingham, UK; Ernest S. Holmes IV, Freeman Children's Hospital, Joplin, MO, USA; Wuh-Liang Hwu, National Taiwan University Hospital, Taipei, Taiwan; Kenneth M. Jaffe, University of Washington, Seattle, WA, USA; Priya Kishnani, Duke University Medical Center, Durham, NC, USA; Tom de Koning and John Wokke, UMC, Utrecht, The Netherlands; Nancy Leslie, Cincinnati Children's Hospital, Cinncinati, OH, USA; A M Lund, Juliane Marie Centre, Copenhagen, Denmark; Jan-Eric Månsson, Sahlgren's University Hospital, Mölndal, Sweden; L Van Maldergem, Institute of Pathology and Genetics, Gerpinnes, Belgium; Suely Kazue Nagahashi Marie, University of Saõ Paulo, Saõ Paulo, Brazil; Gert Matthijs, KUL, Leuven, Belgium; Irene Mavridou and Helen Michelakakis, Institute of Child Health, Athens, Greece; N Muntjewerff, Academic Hospital, Maastricht, The Netherlands; Paul Nelson, Womens and Childrens Hospital, Adelaide, Australia; Mary Nevins, Adirondak Pediatrics, Glenns Falls, NY, USA; Alan Pestronk, Washington University School of Medicine, St. Louis, MO, USA; Barbara Plecko, University of Graz, Graz, Austria; J Rake, Academic Hospital, Groningen, The Netherlands; Paul Rees, Great Ormond Street Hospital, London, UK; Barry Rosenbloom, Tower Hematology Oncology Group, Beverly Hills, CA, USA; Sue Ann Smith, Oregon Healthand Science University, Portland, OR, USA; Katrien Storm and Wim Wuyts, Center of Medical Genetics, Wilrijk, Belgium; Soroush Tahmasebi and SR Ghaffari, Teheran University, Teheran, Iran; Mark Tarnopolsky, McMaster University Medical Center, Hamilton, Canada; Matthew Taylor, University of Colorado Hospital, Aurora, CO, USA; Peter Turnpenny, Royal Devon and Exeter Hospital (Heavitree), Exeter, UK; Christine Verellen, Center of Human Genetics, Brussels, Belgium; Johan Van Hove, University Hospital Gasthuisberg, Leuven, Belgium; Ed Wraith, Royal Manchester Children's Hospital, Manchester, UK.


Pompe disease was named after the Dutch pathologist Dr JC Pompe who reported about a deceased infant with idiopathic hypertrophy of the heart. The clinical findings were failure to thrive, generalized muscle weakness and cardio-respiratory failure. The key pathologic finding was massive storage of glycogen in heart, skeletal muscle and many other tissues. The disease was classified as glycogen storage disease type II and decades later shown to be a lysosomal disorder caused by acid α-glucosidase deficiency. The clinical spectrum of Pompe disease appeared much broader than originally recognized. Adults with the same enzyme deficiency, alternatively named acid maltase deficiency, were reported to have slowly progressive skeletal muscle weakness and respiratory problems, but no cardiac involvement. The clinical heterogeneity is largely explained by the kind and severity of mutations in the acid α-glucosidase gene (GAA), but secondary factors, as yet unknown, have a substantial impact. The Pompe disease mutation database aims to list all GAA sequence variations and describe their effect. This update with 107 sequence variations (95 being novel) brings the number of published variations to 289, the number of non-pathogenic mutations to 67 and the number of proven pathogenic mutations to 197. Further, this article introduces a tool to rate the various mutations by severity, which will improve understanding of the genotype-phenotype correlation and facilitate the diagnosis and prognosis in Pompe disease. © 2008 Wiley-Liss, Inc.