Long-term efficacy of hematopoietic stem cell transplantation on brain involvement in patients with mucopolysaccharidosis type II: A nationwide survey in Japan

Akemi Tanaka, Torayuki Okuyama, Yasuyuki Suzuki, Norio Sakai, Hiromitsu Takakura, Tomo Sawada, Toju Tanaka, Takanobu Otomo, Toya Ohashi, Mika Ishige-Wada, Hiromasa Yabe, Toshihiro Ohura, Nobuhiro Suzuki, Koji Kato, Souichi Adachi, Ryoji Kobayashi, Hideo Mugishima, Shunichi Kato

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84 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)513-520
Number of pages8
JournalMolecular Genetics and Metabolism
Volume107
Issue number3
DOIs
Publication statusPublished - Nov 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

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