Assessment of Activity of Daily Life in Mucopolysaccharidosis Type II Patients with Hematopoietic Stem Cell Transplantation.

Yasuyuki Suzuki,Toshiyuki Fukao,Shunji Tomatsu,Tadao Orii,Madeleine Taylor,Kenji Orii

doi:10.3390/diagnostics10010046

Abstract

The effectiveness of hematopoietic stem cell transplantation (HSCT) for mucopolysaccharidosis type II (MPS II, Hunter disease) remains controversial although recent studies have shown HSCT provides more clinical impact. This study aims to evaluate the long-term effectiveness of HSCT using the activity of daily living (ADL) scores in patients with MPS II. Sixty-nine severely affected MPS II patients (19 patients who received HSCT and 50 untreated patients) and 40 attenuated affected patients (five with HSCT and 35 untreated) were investigated by a simplified ADL questionnaire. The frequency of clinical findings and the scores of ADL (verbal, gross motor, and the level of care) were analyzed statistically. The mean age of onset of 19 severely affected patients who received HSCT was 1.40 years ± 1.06, which is not statistically different from that of 50 untreated patients (p = 0.11). Macroglossia, frequent airway infection, hepatosplenomegaly, joint contracture, and sleep apnea were less frequent in the HSCT-treated group of severe MPS II patients. The severe phenotype HSCT treated group reported a statistically significant higher score of verbal function and gross motor function between the ages of 10 and 15 years and a higher level of care score between 10 and 20 years. Patients with the attenuated phenotype showed high ADL scores, and all of five HSCT treated patients reported a lower frequency of frequent airway infection, coarse skin, umbilical/inguinal hernia, hepatosplenomegaly, heart valve disorders, and carpal tunnel. In conclusion, HSCT is effective, resulting in improvements in clinical features and ADL in patients with MPS II. HSCT should be re-reviewed as a therapeutic option for MPS II patients.

Highlights

Mucopolysaccharidosis (MPS II, Hunter disease, iduronate-2-sulfatase deficiency, OMIM #309900)is a lysosomal storage disorder with X-linked recessive inheritance characterized by the systemic manifestations such as short stature, multiple joint contractures, dysmorphic face, airway narrowing and infection, heart valve disorders, hepatosplenomegaly, visual and hearing difficulties and neurologic disabilities [1,2]
We have investigated the effectiveness of hematopoietic stem cell transplantation (HSCT) for patients with MPS II, using a simplified activity of daily living (ADL) questionnaire in Japan
Our finding further demonstrates that HSCT improved clinical manifestations and ADL of the patients with the severe phenotype

Summary

Introduction

Mucopolysaccharidosis (MPS II, Hunter disease, iduronate-2-sulfatase deficiency, OMIM #309900)is a lysosomal storage disorder with X-linked recessive inheritance characterized by the systemic manifestations such as short stature, multiple joint contractures, dysmorphic face, airway narrowing and infection, heart valve disorders, hepatosplenomegaly, visual and hearing difficulties and neurologic disabilities [1,2]. Patients with the severe phenotype show cognitive impairment and neurological deterioration that lead to the early death before adulthood, whereas patients with the attenuated phenotype usually manifest progressive cardiopulmonary insufficiency, hearing impairment, and gradual decrease of the activity of daily living (ADL) in the adulthood. Hematopoietic stem cell transplantation (HSCT) had been widely performed as a therapeutic approach for patients with MPS I (Hurler syndrome) since the 1980s [3,4]. HSCT for patients with MPS II has been controversial, and the early studies suggest that HSCT is not effective for MPS II [5,6]. In 2017 reported the effects of HSCT on 146 MPS II patients.

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