title: Effects of a higher dose of alglucosidase alfa on ventilator-free survival and motor outcome in classic infantile Pompe disease: an open-label single-center study.
abstract: Though enzyme-replacement therapy (ERT) with alglucosidase alfa has significantly improved the prospects for patients with classic infantile Pompe disease, some 50 % of treated infants do not survive ventilator-free beyond the age of 3 years. We investigated whether higher and more frequent dosing of alglucosidase alfa improves outcome.
  
  
  
  Eight cross-reactive immunological material (CRIM) positive patients were included in the study. All had fully deleterious mutations in both GAA alleles. Four received a dose of 20 mg/kg every other week (eow) and four received 40 mg/kg/week. Survival, ventilator-free survival, left-ventricular mass index (LVMI), motor outcome, infusion-associated reactions (IARs), and antibody formation were evaluated.
  
  
  
  All eight patients were alive at study end, seven of them remained ventilator-free. The patient who became ventilator dependent was treated with 20 mg/kg eow. Three of the four patients receiving 20 mg/kg eow learned to walk; two of them maintained this ability at study end. All four patients receiving 40 mg/kg/week acquired and maintained the ability to walk at study end (ages of 3.3-5.6 years), even though their baseline motor functioning was poorer. There were no apparent differences between the two dose groups with respect to the effect of ERT on LVMI, the number of IARs and antibody formation.
  
  
  
  Our data may suggest that a dose of 40 mg/kg/week improves outcome of CRIM positive patients over that brought by the currently recommended dose of 20 mg/kg eow. Larger studies are needed to draw definite conclusions.
authors.affiliation: Department of Pediatrics, Division of Metabolic Diseases and Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Dr Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands.
authors.forename: C M
authors.initials: CM
authors.lastname: van Gelder
authors.affiliation: Department of Pediatrics, Division of Metabolic Diseases and Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Dr Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Poelman
authors.affiliation: Department of Pediatrics, Division of Metabolic Diseases and Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Dr Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Plug
authors.affiliation: Department of Clinical Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Hoogeveen-Westerveld
authors.affiliation: Department of Pediatrics, Division of Metabolic Diseases and Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Dr Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands.|Department of Neurology, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: N A M E
authors.initials: NAME
authors.lastname: van der Beek
authors.affiliation: Department of Clinical Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: A J J
authors.initials: AJJ
authors.lastname: Reuser
authors.affiliation: Department of Pediatrics, Division of Metabolic Diseases and Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Dr Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands. a.vanderploeg@erasmusmc.nl.
authors.forename: A T
authors.initials: AT
authors.lastname: van der Ploeg
mesh_terms: D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions / Q000502:physiology; D056947:Enzyme Replacement Therapy / Q000379:methods; D005260:Female; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016896:Treatment Outcome; D012122:Ventilators, Mechanical; D000520:alpha-Glucosidases / Q000627:therapeutic use*
chemical_list: C509951:GAA protein, human; D000520:alpha-Glucosidases