Newborn screening for Gaucher disease in Japan

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

PMID: 35242582

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

Highlights: The prevalence of Gaucher disease (GD) using newborn screening (NBS) was 1 in 77,720 in Japan, which was higher than previously estimated frequency.

Abstract

Background: 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 nonneuronopathic and neuronopathic GD may be challenging as the two sometimes phenotypically overlap.

Purpose: 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.

Methods: NBS was performed for Fabry disease, Pompe disease, and GD, mainly in the Kyushu area in Japan. The results of NBS for GD, as well as, the insights gained from following the clinical course of patients diagnosed through NBS was discussed.

Results: A total of 155,442 newborns were screened using an enzyme activity assay using dried blood spots. Four newborns showing lower GCase activity were found 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.

Conclusion: 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.