title: Early treatment with laronidase improves clinical outcomes in patients with attenuated MPS I: a retrospective case series analysis of nine sibships.
abstract: BACKGROUND
  Enzyme replacement therapy (ERT) with laronidase, (recombinant human α-L-iduronidase; Aldurazyme) is the primary treatment option for patients with attenuated mucopolysaccharidosis type I (MPS I). This study examined the effect of early ERT on clinical manifestations.
  
  
  METHODS
  This multinational, retrospective case series abstracted data from records of 20 patients with Hurler-Scheie syndrome within nine sibships that included older siblings treated with laronidase after the development of significant clinical symptoms, and younger siblings treated before significant symptomatology. Median age at diagnosis was 5.6 and 0.5 years for older and younger siblings, respectively. Median age at ERT initiation was 7.9 and 1.9 years for older and younger siblings, respectively.
  
  
  RESULTS
  Improvement or stabilization of somatic signs and symptoms was more notable in younger siblings. Organomegaly present at onset of ERT improved in the majority of both older and younger siblings. Analysis of physician-rated symptom severity demonstrated that cardiac, musculoskeletal, and cognitive symptoms, when absent or mild in younger siblings at ERT initiation, generally did not develop or progress. The majority of older siblings had height/length Z-scores greater than two standard deviations below the mean (less than -2) at both time points. In general, Z-scores for younger siblings were closer to the sex- and age-matched means at follow-up.
  
  
  CONCLUSIONS
  These findings suggest early initiation of laronidase, prior to the onset of symptoms in patients with attenuated MPS I, can slow or prevent the development of severe clinical manifestations.
authors.affiliation: Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia.
authors.forename: Nouriya A
authors.initials: NA
authors.lastname: Al-Sannaa
authors.affiliation: Department of Inherited Errors of Metabolism, Hospital Juan P. Garrahan, Buenos Aires, Argentina.
authors.forename: Luisa
authors.initials: L
authors.lastname: Bay
authors.affiliation: Dr. John T. Macdonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Barbouth
authors.affiliation: Pediatric Services, Robert Boulin Hospital, Libourne, France.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Benhayoun
authors.affiliation: CHU Bordeaux, Pellegrin Hospital, Department and Univ. Bordeaux, laboratoire MRGM (EA4576), Bordeaux, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Goizet
authors.affiliation: Metabolic Section, Children's Hospital of Córdoba, Córdoba, Argentina.
authors.forename: Norberto
authors.initials: N
authors.lastname: Guelbert
authors.affiliation: Manchester Centre for Genomic Medicine, St. Mary's Hospital, CMFT, University of Manchester, Manchester, UK.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Jones
authors.affiliation: Reference Center for Inborn Errors of Metabolism, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Sandra Obikawa
authors.initials: SO
authors.lastname: Kyosen
authors.affiliation: Reference Center for Inborn Errors of Metabolism, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Martins
authors.affiliation: Division of Human Genetics, Department of Pediatrics, Hasbro Children's Hospital, Brown University, Providence, RI, USA.
authors.forename: Chanika
authors.initials: C
authors.lastname: Phornphutkul
authors.affiliation: Pediatric Division, General Hospital of Segovia, Segovia, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Reig
authors.affiliation: Genzyme, a Sanofi company, 500 Kendall Street, Cambridge, MA, 02142, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Pleat
authors.affiliation: Genzyme, a Sanofi company, 500 Kendall Street, Cambridge, MA, 02142, USA.|Pfizer Inc, New York City, NY, USA.
authors.forename: Shari
authors.initials: S
authors.lastname: Fallet
authors.affiliation: Genzyme, a Sanofi company, 500 Kendall Street, Cambridge, MA, 02142, USA. Iva.IvanovskaHolder@genzyme.com.
authors.forename: Iva
authors.initials: I
authors.lastname: Ivanovska Holder
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007068:Iduronidase / Q000627:therapeutic use*; D007223:Infant; D038622:Internationality; D008297:Male; D008059:Mucopolysaccharidosis I / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000235:genetics; D011859:Radiography; D012189:Retrospective Studies; D035781:Siblings; D016896:Treatment Outcome
chemical_list: D007068:Iduronidase