Activities of daily living in patients with Hunter syndrome: Impact of enzyme replacement therapy and hematopoietic stem cell transplantationby Julian Tanjuakio, Yasuyuki Suzuki, Pravin Patel, Eriko Yasuda, Francyne Kubaski, Akemi Tanaka, Hiromasa Yabe, Robert W. Mason, Adriana M. Montaño, Kenji E. Orii, Koji O. Orii, Toshiyuki Fukao, Tadao Orii, Shunji Tomatsu

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Activities of daily living in patients with Hunter syndrome: Impact of poietic stem

Julian Tanjuakio a,1, Yasuyuki Suzu

Hiromasa Yabe e, Robert W. Mason

Tadao Orii i, Shunji Tomatsu a,i,⁎⁎ a Nemours/Alfred I. duPont Hospital for Children, Wilmingto b Medical Education Development Center, Gifu University, G c Department of Biological Sciences, University of Delaware, d raduate sity Schoo t. Louis, M gy, St. Lou iversity H f Medicin

Received in revised form 31 October 2014

We devised a new ADL questionnaire with three domains: “movement,” “movement with cognition,” and “cogr Inc. All rights reserved.

Molecular Genetics and Metabolism 114 (2015) 161–169

Contents lists available at ScienceDirect

Molecular Genetics j ourna l homepage: www.e ls1. Introduction

Hunter syndrome (mucopolysaccharidosis II; MPS II) is an X⁎ Correspondence to: Y. Suzuki, Medical Education Development Center, Gifu

University, Yanagido-1-1, Gifu 501-1194, Japan.© 2014 ElsevieKeywords:

Enzyme replacement therapy

Hematopoietic stem cell transplantation

Activities of daily living

Hunter syndrome

Clinical phenotype nition.” 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 patientswithHunter 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 (N8 years), and 4 untreated patients. Among 18 severe phenotypic patients treated by

HSCT, 10 were designated as early HSCT (≤5 years), while 8 were designated as late HSCT (N5 years).

Scores from patients with severe phenotypes were lower than controls and attenuated phenotypes in all categories. Among patients with severe phenotypes, therewas 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.⁎⁎ Correspondence to: S. Tomatsu, Skeletal Dysplasia L

Research, Nemours/Alfred I. duPont Hospital for C

Wilmington, DE. 19899-0269. Fax: +1 302 651 6888.

E-mail addresses: (Y. Suzuki), stoma (S. Tomatsu). 1 The first two authors should be regarded as joint first 1096-7192/© 2014 Elsevier Inc. All rights reserved.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.Accepted 1 November 2014

Available online 8 November 2014Department of Pediatrics, Osaka City University G e Department of Cell Transplantation, Tokai Univer f Department of Pediatrics, Saint Louis University, S g Department of Biochemistry and Molecular Biolo h Division of Neonatal Intensive Care Unit, Gifu Un i Department of Pediatrics, Gifu University, School o a r t i c l e i n f o

Article history:

Received 2 September 2014ki b,⁎,1, Pravin Patel a, Eriko Yasuda a, Francyne Kubaski a,c, Akemi Tanaka d, a, Adriana M. Montaño f,g, Kenji E. Orii h, Koji O. Orii i, Toshiyuki Fukao i, n, DE, USA ifu, Japan

Newark, DE, USA

School of Medicine, Osaka, Japan l of Medicine, Isehara, Japan

O 63104, USA is, MO 63104, USA ospital, Gifu, Japan e, Gifu, Japan a b s t r a c t

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 tocell transplantation enzyme replacement therapy and hematoab, Department of Biomedical hildren, 1600 Rockland Rd.,, authors.and Metabolism ev ie r .com/ locate /ymgmelinked recessive lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase (IDS). IDS is required for the degradation of the glycosaminoglycans (GAGs), dermatan sulfate (DS), and heparan sulfate (HS). Deficiency of this enzyme results in the accumulation of

GAG in most cell types and tissues, leading to the progressive damage 162 J. Tanjuakio et al. / Molecular Genetics and Metabolism 114 (2015) 161–169to the bone, cartilage, upper and lower respiratory tract, lung, heart, and brain. Clinical manifestations include coarse facial feature, umbilical hernia, inguinal hernia, marked Mongolian spots, obstructive airway disease, recurrent nose and ear infections, and skeletal deformities [1].

Patients commonly show initial excessive growth in the first few years followed by growth retardation, umbilical hernia, inguinal hernia, and thick bones [1]. In Asian populations, an early sign is appearance of a prominent Mongolian spot [2]. Ultrastructural findings of Mongolian spots suggest that the hyperpigmentation is a long-lasting symptom.

Detection of Mongolian spots may lead to early diagnosis in patients with a mild form of Hunter syndrome [2].

Clinical cases of Hunter syndrome are ranked on a continuum fromattenuated phenotypes to severe phenotypes. Severe and attenuated phenotypes are differentiated by the presence or absence of cognitive impairment. The severe phenotype of Hunter syndrome, which is twice as prevalent as the attenuated form, is characterized by significant CNS involvement such asmental retardation and loss of cognitive function [3–7].

Untreated patients usually do not survive past their second decade of life [1,3]. Patients with attenuated phenotypes are mainly characterized by somatic involvement without CNS involvement. Surgical operations of umbilical/inguinal hernia repair, tonsillectomy, adenoidectomy, and ear tubes are common in Hunter syndrome [1,8,9]. Risk factors of mortality in patients with Hunter syndrome include severe upper airway constriction and abnormal heart development causing left and right ventricular hypertrophy, heart valvular involvement, and heart failure [1,9].