Newborn screening for Gaucher disease in Japan

Takaaki Sawada; Jun Kido; Keishin Sugawara; Shinichiro Yoshida; Shirou Matsumoto; Tomoyuki Shimazu; Yuki Matsushita; Takahito Inoue; Shinichi Hirose; Fumio Endo; Kimitoshi Nakamura

doi:10.1016/j.ymgmr.2022.100850

Newborn screening for Gaucher disease in Japan

Mol Genet Metab Rep. 2022 Feb 18:31:100850. doi: 10.1016/j.ymgmr.2022.100850. eCollection 2022 Jun.

Authors

Affiliations

¹ Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
² Department of Pediatrics, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
³ KM Biologics Co., Ltd, Kumamoto, Japan.
⁴ Department of Pediatrics, National Hospital Organization Kumamoto Saishun Medical Center, Kumamoto, Japan.
⁵ Department of Pediatrics, Clinical Research Institute, Kyushu Medical Center, National Hospital Organization, Fukuoka, Japan.
⁶ Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Japan.
⁷ Department of Pediatrics, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
⁸ General Medical Research Center, School of Medicine, Fukuoka University, Fukuoka, Japan.
⁹ Kumamoto-Ezuko Medical Center for Disabled Children, Kumamoto, Japan.

Abstract

Gaucher disease (GD) is an autosomal recessive inborn metabolic disorder caused by a glucocerebrosidase (GCase) defect. GD is classified into three main types depending on accompanying neurological symptoms. Enzyme replacement therapy and substrate reduction therapy are limited in the treatment of neurological symptoms, and using genotype and GCase activity to discriminate between non-neuronopathic and neuronopathic GD may be challenging as the two sometimes phenotypically overlap. The number of patients exhibiting neurological symptoms in Japan is significantly higher than that in Europe and the United States, and newborn screening (NBS) is still not actively performed in Japan. Definitive determination of the actual frequency and proportion of the type of GD from the results of NBS remains inconclusive. We performed NBS for Fabry disease, Pompe disease, and GD, mainly in the Kyushu area in Japan. Herein, we discuss the results of NBS for GD, as well as, the insights gained from following the clinical course of patients diagnosed through NBS. A total of 155,442 newborns were screened using an enzyme activity assay using dried blood spots. We found four newborns showing lower GCase activity and were definitively diagnosed with GD by GBA gene analysis. The frequency of GD diagnosis through NBS was 1 in 77,720 when limited to the probands. This frequency is higher than that previously estimated in Japan. In the future, NBS for GD is expected to be performed in many regions of Japan and contribute to detecting more patients with GD. Early screening and diagnosis may have a very significant impact on the quality of life and potentially longevity in infants with GD.

Keywords: Enzyme replacement therapy; Gaucher disease; Glucocerebrosidase; Neuronopathic Gaucher disease; Newborn screening.