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.
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.
Authors: Miroslav Merta; Jana Reiterova; Jana Ledvinova; Helena Poupetová; Robert Dobrovolny; Romana Rysavá; Dita Maixnerová; Jan Bultas; Jirí Motán; Jitka Slivkova; Doris Sobotova; Jana Smrzova; Vladimir Tesar Journal: Nephrol Dial Transplant Date: 2006-10-13 Impact factor: 5.992
Authors: Soumeya Bekri; Adrian Enica; Thomas Ghafari; Gisèle Plaza; Isabelle Champenois; Gabriel Choukroun; Robert Unwin; Philippe Jaeger Journal: Nephron Clin Pract Date: 2005-05-09
Authors: M Tanaka; T Ohashi; M Kobayashi; Y Eto; N Miyamura; K Nishida; E Araki; K Itoh; K Matsushita; M Hara; K Kuwahara; T Nakano; N Yasumoto; H Nonoguchi; K Tomita Journal: Clin Nephrol Date: 2005-10 Impact factor: 0.975
Authors: Peter Kotanko; Reinhard Kramar; Danijela Devrnja; Eduard Paschke; Till Voigtländer; Martin Auinger; Severo Pagliardini; Marco Spada; Klaus Demmelbauer; Matthias Lorenz; Anna-Christine Hauser; Hans-Jörg Kofler; Karl Lhotta; Ulrich Neyer; Wolfgang Pronai; Manfred Wallner; Clemens Wieser; Martin Wiesholzer; Herbert Zodl; Manuela Födinger; Gere Sunder-Plassmann Journal: J Am Soc Nephrol Date: 2004-05 Impact factor: 10.121
Authors: C Whybra; C Kampmann; F Krummenauer; M Ries; E Mengel; E Miebach; F Baehner; K Kim; M Bajbouj; A Schwarting; A Gal; M Beck Journal: Clin Genet Date: 2004-04 Impact factor: 4.438
Authors: Susana Ferreira; Christiane Auray-Blais; Michel Boutin; Pamela Lavoie; José Pedro Nunes; Elisabete Martins; Scott Garman; João Paulo Oliveira Journal: Clin Chim Acta Date: 2015-06-09 Impact factor: 3.786