Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis

Hiroki Maruyama, Kaori Miyata, Mariko Mikame, Atsumi Taguchi, Chu Guili, Masaru Shimura, Kei Murayama, Takeshi Inoue, Saori Yamamoto, Koichiro Sugimura, Koichi Tamita, Toshihiro Kawasaki, Jun Kajihara, Akifumi Onishi, Hitoshi Sugiyama, Teiko Sakai, Ichijiro Murata, Takamasa Oda, Shigeru Toyoda, Kenichiro HanawaTakeo Fujimura, Shigehisa Ura, Mimiko Matsumura, Hideki Takano, Satoshi Yamashita, Gaku Matsukura, Ryushi Tazawa, Tsuyoshi Shiga, Mio Ebato, Hiroshi Satoh, Satoshi Ishii

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Purpose: Plasma globotriaosylsphingosine (lyso-Gb3) is a promising secondary screening biomarker for Fabry disease. Here, we examined its applicability as a primary screening biomarker for classic and late-onset Fabry disease in males and females. Methods: Between 1 July 2014 and 31 December 2015, we screened 2,360 patients (1,324 males) referred from 169 Japanese specialty clinics (cardiology, nephrology, neurology, and pediatrics), based on clinical symptoms suggestive of Fabry disease. We used the plasma lyso-Gb3 concentration, α-galactosidase A (α-Gal A) activity, and analysis of the α-Gal A gene (GLA) for primary and secondary screens, respectively. Results: Of 8 males with elevated lyso-Gb3 levels (≥2.0 ng ml–1) and low α-Gal A activity (≤4.0 nmol h–1 ml–1), 7 presented a GLA mutation (2 classic and 5 late-onset). Of 15 females with elevated lyso-Gb3, 7 displayed low α-Gal A activity (5 with GLA mutations; 4 classic and 1 late-onset) and 8 exhibited normal α-Gal A activity (1 with a classic GLA mutation and 3 with genetic variants of uncertain significance). Conclusion: Plasma lyso-Gb3 is a potential primary screening biomarker for classic and late-onset Fabry disease probands.

Original languageEnglish
Pages (from-to)44-52
Number of pages9
JournalGenetics in Medicine
Volume21
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

Keywords

  • Fabry disease
  • gene analysis
  • genetic variants of uncertain significance
  • lyso-Gb3
  • screening

ASJC Scopus subject areas

  • Genetics(clinical)

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    Maruyama, H., Miyata, K., Mikame, M., Taguchi, A., Guili, C., Shimura, M., Murayama, K., Inoue, T., Yamamoto, S., Sugimura, K., Tamita, K., Kawasaki, T., Kajihara, J., Onishi, A., Sugiyama, H., Sakai, T., Murata, I., Oda, T., Toyoda, S., ... Ishii, S. (2019). Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis. Genetics in Medicine, 21(1), 44-52. https://doi.org/10.1038/gim.2018.31