title: An individually, modified approach to desensitize infants and young children with Pompe disease, and significant reactions to alglucosidase alfa infusions.
abstract: OBJECTIVE
  Pompe disease (PD) is a progressive metabolic myopathy for which the only available treatment is alglucosidase alfa (Myozyme®). Enzyme replacement therapy (ERT) has improved ventilator-free survival, and cardiac and motor functions in patients with infantile PD. However, for an adequate response to occur, a large amount of enzymes must be infused. In some patients, this may be problematic due to infusion-associated reactions (IARs) occurring in approximately 50% of patients receiving alglucosidase alfa infusions. Whilst the majority of these reactions are mild, life threatening hypersensitivity reactions may occur in some patients. In these patients desensitization is indicated to enable continued ERT safely. Infants and young children with PD and significant infusion reactions pose unique management challenges because of their young age, limited communication skills, variable presentation and underlying cardiomyopathy.
  
  
  METHODS
  In 2 patients with PD who experienced significant ERT-related reactions: an infant (IgE positive) and a young child (IgE negative), we implemented a desensitization protocol, that started by administering a reduced dose of alglucosidase alfa (10 mg/kg weekly) instead of the standard (20 mg/kg bi-weekly) using serial micro-dilutions that were individually prepared and delivered in a highly regulated manner based on patients' clinical manifestations and tolerance.
  
  
  RESULTS
  Successful desensitization was achieved in both patients, allowing them to eventually continue to receive the full dose of ERT safely.
  
  
  CONCLUSIONS
  Therapeutic demands in infants and young children with PD need to be tailored according to the patient presentation, and underlying cardiac and fluid-volume status. Desensitization allowed both patients to continue alglucosidase alfa treatment at the recommended dose without prolonged interruption of therapy, or further reactions.
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, Duke University Medical, Center, Durham, NC 27710, USA.
authors.forename: Areeg H
authors.initials: AH
authors.lastname: El-Gharbawy
authors.forename: Joanne
authors.initials: J
authors.lastname: Mackey
authors.forename: Stephanie
authors.initials: S
authors.lastname: DeArmey
authors.forename: Greg
authors.initials: G
authors.lastname: Westby
authors.forename: Sherry G
authors.initials: SG
authors.lastname: Grinnell
authors.forename: Peggy
authors.initials: P
authors.lastname: Malovrh
authors.forename: Robert
authors.initials: R
authors.lastname: Conway
authors.forename: Priya S
authors.initials: PS
authors.lastname: Kishnani
mesh_terms: D002648:Child; D003888:Desensitization, Immunologic; D056947:Enzyme Replacement Therapy / Q000009:adverse effects*; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D057285:Precision Medicine; D012008:Recurrence; D000520:alpha-Glucosidases / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D007073:Immunoglobulin E; C509951:GAA protein, human; D000520:alpha-Glucosidases