title: Activities of daily living in patients with Hunter syndrome: impact of enzyme replacement therapy and hematopoietic stem cell transplantation.
abstract: The aim of this study was to assess the activities of daily living (ADL) in patients with Hunter syndrome (mucopolysaccharidosis II; MPS II) using a newly designed ADL questionnaire. We applied the questionnaire to evaluate clinical phenotypes and therapeutic efficacies of enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT). We also explored early signs and symptoms to make early diagnosis feasible. We devised a new ADL questionnaire with three domains: "movement," "movement with cognition," and "cognition." Each domain has four subcategories rated on a 5-point scale based on level of assistance. We also scored signs and symptoms unique to MPS by 12 subcategories (five points per category), providing 60 points in total. The questionnaire was first administered to 138 healthy Japanese controls (0.33-50 years), and successively, to 74 Japanese patients with Hunter syndrome (4-49 years). The patient cohort consisted of 51 severe and 23 attenuated phenotypes; 20 patients treated with HSCT, 23 patients treated early with ERT (≤8 years), 25 patients treated late with ERT (>8 years), and 4 untreated patients. Among 18 severe phenotypic patients treated by HSCT, 10 were designated as early HSCT (≤5years), while 8 were designated as late HSCT (>5years). Scores from patients with severe phenotypes were lower than controls and attenuated phenotypes in all categories. Among patients with severe phenotypes, there was a trend that HSCT provides a higher ADL score than early ERT, and there was a significant difference in ADL scores between late ERT and HSCT groups. Early ERT and early HSCT provided a higher score than late ERT and late HSCT, respectively. In conclusion, we have evaluated the feasibility of a new questionnaire in control population and patients with Hunter syndrome, leading to a novel evaluation method for clinical phenotypes and therapeutic efficacy. Early treatment with HSCT provides a better consequence in ADL of patients.
authors.affiliation: Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Tanjuakio
authors.affiliation: Medical Education Development Center, Gifu University, Gifu, Japan. Electronic address: ysuz@gifu-u.ac.jp.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
authors.forename: Pravin
authors.initials: P
authors.lastname: Patel
authors.affiliation: Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
authors.forename: Eriko
authors.initials: E
authors.lastname: Yasuda
authors.affiliation: Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA; Department of Biological Sciences, University of Delaware, Newark, DE, USA.
authors.forename: Francyne
authors.initials: F
authors.lastname: Kubaski
authors.affiliation: Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Department of Cell Transplantation, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yabe
authors.affiliation: Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Mason
authors.affiliation: Department of Pediatrics, Saint Louis University, St. Louis, MO 63104, USA; Department of Biochemistry and Molecular Biology, St. Louis, MO 63104, USA.
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Montaño
authors.affiliation: Division of Neonatal Intensive Care Unit, Gifu University Hospital, Gifu, Japan.
authors.forename: Kenji E
authors.initials: KE
authors.lastname: Orii
authors.affiliation: Department of Pediatrics, Gifu University, School of Medicine, Gifu, Japan.
authors.forename: Koji O
authors.initials: KO
authors.lastname: Orii
authors.affiliation: Department of Pediatrics, Gifu University, School of Medicine, Gifu, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukao
authors.affiliation: Department of Pediatrics, Gifu University, School of Medicine, Gifu, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Orii
authors.affiliation: Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA; Department of Pediatrics, Gifu University, School of Medicine, Gifu, Japan. Electronic address: stomatsu@nemours.org.
authors.forename: Shunji
authors.initials: S
authors.lastname: Tomatsu
mesh_terms: D000203:Activities of Daily Living; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003071:Cognition; D056947:Enzyme Replacement Therapy / Q000592:standards; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007068:Iduronidase / Q000627:therapeutic use; D007223:Infant; D007564:Japan; D008297:Male; D008875:Middle Aged; D016532:Mucopolysaccharidosis II / Q000175:diagnosis / Q000628:therapy*; D010641:Phenotype; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D007068:Iduronidase
keywords: Activities of daily living; Clinical phenotype; Enzyme replacement therapy; Hematopoietic stem cell transplantation; Hunter syndrome