Frequency of iduronate-2-sulfatase gene variants detected in newborn screening for mucopolysaccharidosis type II in Japan

Yusuke Hattori; Takaaki Sawada; Jun Kido; Keishin Sugawara; Shinichiro Yoshida; Shirou Matsumoto; Takahito Inoue; Shinichi Hirose; Kimitoshi Nakamura

doi:10.1016/j.ymgmr.2023.101003

Frequency of iduronate-2-sulfatase gene variants detected in newborn screening for mucopolysaccharidosis type II in Japan

Mol Genet Metab Rep. 2023 Aug 28:37:101003. doi: 10.1016/j.ymgmr.2023.101003. eCollection 2023 Dec.

Authors

Yusuke Hattori^{1

2}, Takaaki Sawada^{2

3}, Jun Kido^{2

3}, Keishin Sugawara³, Shinichiro Yoshida⁴, Shirou Matsumoto^{2

3}, Takahito Inoue^{5

6}, Shinichi Hirose⁷, Kimitoshi Nakamura^{2

3}

Affiliations

¹ Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
² Department of Pediatrics, Kumamoto University Hospital, Kumamoto, Japan.
³ Department of Pediatrics, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
⁴ KM Biologics Co., Ltd., Kumamoto, Japan.
⁵ Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Japan.
⁶ Department of Pediatrics, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
⁷ General Medical Research Center, School of Medicine, Fukuoka University, Fukuoka, Japan.

Abstract

Mucopolysaccharidosis II (MPS II) is an X-linked, recessive, inborn metabolic disorder caused by defects in iduronate-2-sulfatase (IDS). The age at onset, disease severity, and rate of progression vary significantly among patients. This disease is classified into severe or mild forms depending on neurological symptom involvement. The severe form is associated with progressive cognitive decline while the mild form is predominantly associated with somatic features. Newborn screening (NBS) for MPS II has been performed since December 2016, mainly in Kyushu, Japan, where 197,700 newborns were screened using a fluorescence enzyme activity assay of dried blood spots. We diagnosed one newborn with MPS II with lower IDS activity, elevated urinary glycosaminoglycans, and a novel variant of the IDS gene. In the future, NBS for MPS II is expected to be performed in many regions of Japan and will contribute to the detection of more patients with MPS II, which is crucial to the early treatment of the disorder.

Keywords: Enzyme replacement therapy; Hunter syndrome; Iduronate-2-sulfatase; Mucopolysaccharidosis type II; Newborn screening.