Plasma Globotriaosylsphingosine and α-Galactosidase A Activity as a Combined Screening Biomarker for Fabry Disease in a Large Japanese Cohort

Current Issues in Molecular Biology

Norio Sakai¹  Hiroshi Satoh²  Satoshi Yamashita³  Kenji Yamabe⁴  Shigeru Toyoda⁵  Mariko Mikame⁶  Atsumi Taguchi⁶  Hiroki Maruyama⁶  Michihiro Hosojima⁷  Yumi Ito⁸  Hitoshi Sugiyama⁹  Akifumi Onishi^1,10  Toshiyuki Seto^1,11  Naoki Morito^1,12  Kazufumi Izaki^1,13  Yukio Yokoyama^1,14  Satoshi Ishii^1,15  Ryushi Tazawa^1,16  Atsushi Izawa^1,17 

[1] Child Healthcare and Genetic Science Laboratory, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita 565-0871, Japan;Department of Cardiology, Fujinomiya City Hospital, Fujinomiya 418-0076, Japan;Department of Cardiology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan;Department of Cardiology, Toyooka Hospital, Toyooka 668-8501, Japan;Department of Cardiovascular Medicine, Dokkyo Medical University, Mibu 321-0293, Japan;Department of Clinical Nephroscience, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan;Department of Clinical Nutrition Science, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan;Department of Health Promotion Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan;Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama 700-8558, Japan;Department of Internal Medicine, Fukuyama City Hospital, Fukuyama 721-8511, Japan;Department of Medical Genetics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan;Department of Nephrology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan;Department of Pediatrics, Yao Municipal Hospital, Yao 581-0069, Japan;Division of Nephrology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima 730-8619, Japan;GlycoPharma Corporation, Oita 870-0822, Japan;Health Administration Center, Student Support and Health Administration Organization, Tokyo Medical and Dental University, Bunkyo-ku 113-8510, Japan;School of Health Sciences, Shinshu University, Matsumoto 390-8621, Japan;

关键词: globotriaosylsphingosine;    late-onset biopsy-proven Fabry disease;    saposin;    gene analysis;    aberrant splicing transcript;   

DOI  :  10.3390/cimb43010032

来源: DOAJ

【 摘 要 】

Fabry disease is an X-linked disorder of α-galactosidase A (GLA) deficiency. Our previous interim analysis (1 July 2014 to 31 December 2015) revealed plasma globotriaosylsphingosine as a promising primary screening biomarker for Fabry disease probands. Herein, we report the final results, including patients enrolled from 1 January to 31 December 2016 for evaluating the potential of plasma globotriaosylsphingosine and GLA activity as a combined screening marker. We screened 5691 patients (3439 males) referred from 237 Japanese specialty clinics based on clinical findings suggestive of Fabry disease using plasma globotriaosylsphingosine and GLA activity as primary screening markers, and GLA variant status as a secondary screening marker. Of the 14 males who tested positive in the globotriaosylsphingosine screen (≥2.0 ng/mL), 11 with low GLA activity (<4.0 nmol/h/mL) displayed GLA variants (four classic, seven late-onset) and one with normal GLA activity and no pathogenic variant displayed lamellar bodies in affected organs, indicating late-onset biopsy-proven Fabry disease. Of the 19 females who tested positive in the globotriaosylsphingosine screen, eight with low GLA activity displayed GLA variants (six classic, two late-onset) and five with normal GLA activity displayed a GLA variant (one classic) and no pathogenic variant (four late-onset biopsy-proven). The combination of plasma globotriaosylsphingosine and GLA activity can be a primary screening biomarker for classic, late-onset, and late-onset biopsy-proven Fabry disease probands.

【 授权许可】

Unknown