title: Long-term experience with enzyme replacement therapy (ERT) in MPS II patients with a severe phenotype: an international case series.
abstract: BACKGROUND
  No published clinical trial data are available to inform the use of enzyme replacement therapy (ERT) in patients with the severe (neuropathic) phenotype of mucopolysaccharidosis II (MPS II). Current guidelines recommend ERT administered intravenously be used on a trial basis in this population.
  
  
  OBJECTIVE
  A retrospective chart review was conducted at five international centers for this case series of 22 patients with neuropathic MPS II who received intravenous idursulfase 0.5 mg/kg weekly for at least 2 consecutive years. We collected data about urinary glycosaminoglycan levels, adverse events, and the following somatic signs/symptoms: skeletal disease, joint range of motion, liver/spleen size, respiratory infections, cardiac disease, diarrhea, skin/hair texture, and hospitalizations.
  
  
  RESULTS
  The age at diagnosis was 2 months to 5 years, and the age at idursulfase initiation was between 18 months and 21 years. One of 22 patients experienced improvements in seven somatic signs/symptoms; 17/22 experienced improvements in five to six somatic signs/symptoms; and 4/22 experienced improvements in four somatic signs/symptoms. None experienced fewer than four improvements. No new safety concerns arose. Infusion-related reactions were experienced by 4/22 patients but were successfully managed using accepted strategies.
  
  
  CONCLUSIONS
  Long-term treatment with idursulfase was associated with improvements in somatic manifestations in this case series of patients with neuropathic MPS II. The family and medical team should maintain open lines of communication to make treatment decisions that take into consideration the benefits and limitations of ERT in this population.
authors.affiliation: Department of Pediatric and Adolescent Medicine, Villa Metabolica, University Medical Center of Mainz, Mainz, Germany, christina.lampe@hsk-wiesbaden.de.
authors.forename: Christina
authors.initials: C
authors.lastname: Lampe
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Bosserhoff
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Burton
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Carolina F
authors.initials: CF
authors.lastname: de Souza
authors.forename: Camila
authors.initials: C
authors.lastname: Bittar
authors.forename: Nicole
authors.initials: N
authors.lastname: Muschol
authors.forename: Rebecca
authors.initials: R
authors.lastname: Olson
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Mendelsohn
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000209:etiology / Q000523:psychology; D056947:Enzyme Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006025:Glycosaminoglycans / Q000652:urine; D006801:Humans; D007066:Iduronate Sulfatase / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D016532:Mucopolysaccharidosis II / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D009929:Organ Size; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006025:Glycosaminoglycans; D007066:Iduronate Sulfatase; C517982:idursulfase