title: Long-term efficacy of hematopoietic stem cell transplantation on brain involvement in patients with mucopolysaccharidosis type II: a nationwide survey in Japan.
abstract: Hematopoietic stem cell transplantation (HSCT) has not been indicated for patients with mucopolysaccharidosis II (MPS II, Hunter syndrome), while it is indicated for mucopolysaccharidosis I (MPS I) patients <2 years of age and an intelligence quotient (IQ) of ≥ 70. Even after the approval of enzyme replacement therapy for both of MPS I and II, HSCT is still indicated for patients with MPS I severe form (Hurler syndrome). To evaluate the efficacy and benefit of HSCT in MPS II patients, we carried out a nationwide retrospective study in Japan. Activities of daily living (ADL), IQ, brain magnetic resonance image (MRI) lesions, cardiac valvular regurgitation, and urinary glycosaminoglycan (GAG) were analyzed at baseline and at the most recent visit. We also performed a questionnaire analysis about ADL for an HSCT-treated cohort and an untreated cohort (natural history). Records of 21 patients were collected from eight hospitals. The follow-up period in the retrospective study was 9.6 ± 3.5 years. ADL was maintained around baseline levels. Cribriform changes and ventricular dilatation on brain MRI were improved in 9/17 and 4/17 patients, respectively. Stabilization of brain atrophy was shown in 11/17 patients. Cardiac valvular regurgitation was diminished in 20/63 valves. Urinary GAG concentration was remarkably lower in HSCT-treated patients than age-matched untreated patients. In the questionnaire analysis, speech deterioration was observed in 12/19 patients in the untreated cohort and 1/7 patient in HSCT-treated cohort. HSCT showed effectiveness towards brain or heart involvement, when performed before signs of brain atrophy or valvular regurgitation appear. We consider HSCT is worthwhile in early stages of the disease for patients with MPS II.
authors.affiliation: Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan. akemi-chan@med.osaka-cu.ac.jp
authors.forename: Akemi
authors.initials: A
authors.lastname: Tanaka
authors.forename: Torayuki
authors.initials: T
authors.lastname: Okuyama
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Norio
authors.initials: N
authors.lastname: Sakai
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Takakura
authors.forename: Tomo
authors.initials: T
authors.lastname: Sawada
authors.forename: Toju
authors.initials: T
authors.lastname: Tanaka
authors.forename: Takanobu
authors.initials: T
authors.lastname: Otomo
authors.forename: Toya
authors.initials: T
authors.lastname: Ohashi
authors.forename: Mika
authors.initials: M
authors.lastname: Ishige-Wada
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yabe
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ohura
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Suzuki
authors.forename: Koji
authors.initials: K
authors.lastname: Kato
authors.forename: Souichi
authors.initials: S
authors.lastname: Adachi
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Hideo
authors.initials: H
authors.lastname: Mugishima
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kato
mesh_terms: D000203:Activities of Daily Living; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D056947:Enzyme Replacement Therapy; D005260:Female; D006025:Glycosaminoglycans / Q000652:urine; D019538:Health Care Surveys; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007068:Iduronidase / Q000627:therapeutic use; D007564:Japan; D008279:Magnetic Resonance Imaging; D008297:Male; D008944:Mitral Valve Insufficiency / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D016532:Mucopolysaccharidosis II / Q000201:enzymology / Q000473:pathology* / Q000628:therapy*; D012189:Retrospective Studies; D055502:Secondary Prevention; D013995:Time; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006025:Glycosaminoglycans; D007068:Iduronidase