Screening of Male Dialysis Patients for Fabry Disease by Plasma Globotriaosylsphingosine

Abstract

Summary Background and objectives Previous reports of Fabry disease screening in dialysis patients indicate that α-galactosidase A activity alone cannot specifically and reliably identify appropriate candidates for genetic testing; a marker for secondary screening is required. Elevated plasma globotriaosylsphingosine is reported to be a hallmark of classic Fabry disease. The purpose of this study was to examine the usefulness of globotriaosylsphingosine as a secondary screening target for Fabry disease. Design, setting, participants, & measurements This study screened 1453 patients, comprising 50% of the male dialysis patients in Niigata Prefecture between July 1, 2010 and July 31, 2011. Screening for Fabry disease was performed by measuring the plasma α-galactosidase A enzyme activity and the globotriaosylsphingosine concentration, by high-performance liquid chromatography. Genetic testing and genetic counseling were provided. Results A low level of plasma α-galactosidase A activity (≤4.0 nmol/h per milliliter) was observed in 47 patients (3.2%). Of these, 3 (0.2%) had detectable globotriaosylsphingosine levels. These patients all had α-galactosidase A gene mutations: one was p.Y173X and two were the nonpathogenic p.E66Q. The patient with p.Y173X started enzyme replacement therapy. Subsequent screening of his family identified the same mutation in his elder sister and her children. Genetic testing for 33 of the other 44 patients detected 7 patients with p.E66Q. Thus, the plasma lyso-Gb3 screen identified Fabry disease with high sensitivity (100%) and specificity (94.3%). Conclusions Plasma globotriaosylsphingosine is a promising secondary screening target that was effective for selecting candidates for genetic counseling and testing and for uncovering unrecognized Fabry disease cases.

Results of Fabry Disease Screening in Male Pre-End Stage Renal Disease Patients with Unknown Etiology Found Through the Platform of a Chronic Kidney Disease Education Program in a Northern Taiwan Medical Center

“…A couple of studies investigated the frequency of FD in dialysis [12][13][14][22][23][24][25] and the results showed that the average prevalence rate of FD in dialysis was about 0.37% [26]. It was too late to diagnose new FD patients until they were on HD.…”

Prevalence of Fabry disease in dialysis patients: Japan Fabry disease screening study (J-FAST)

“…There are reports on the frequency of Fabry diseaseinduced dialysis patients, but these were not necessarily examined using a sufficient number of dialysis patients [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. With respect to the clinical diagnosis of ESKD in dialysis patients, the frequency of diabetic nephropathy, chronic glomerulonephritis, nephrosclerosis, etc., is high; however, cases in which the clinical diagnosis of ESKD is unknown are also frequent at about 7.8 % in Japan [24].…”

Fabry Nephropathy: An Evidence-Based Narrative Review

“…In this study, the plasma lyso-Gb3 screen identified FD with high sensitivity (100%) and specificity (94.3%), with a prevalence of FD in male dialysis patients of 0.07% [37].…”

“…With a different approach, Maruyama et al [37] performed the first screening of dialysis patients for FD by measuring plasma Gb3 (lyso-Gb3), which has been shown to be clearly increased in the plasma of patients with symptomatic FD [38]. In this study, the plasma lyso-Gb3 screen identified FD with high sensitivity (100%) and specificity (94.3%), with a prevalence of FD in male dialysis patients of 0.07% [37].…”