title: Screening of male dialysis patients for fabry disease by plasma globotriaosylsphingosine.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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: Department of Clinical Nephroscience, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. hirokim@med.niigata-u.ac.jp
authors: Hiroki
authors: H
authors: Maruyama
authors: Takuma
authors: T
authors: Takata
authors: Yutaka
authors: Y
authors: Tsubata
authors: Ryushi
authors: R
authors: Tazawa
authors: Kiyoe
authors: K
authors: Goto
authors: Jun
authors: J
authors: Tohyama
authors: Ichiei
authors: I
authors: Narita
authors: Hidekatsu
authors: H
authors: Yoshioka
authors: Satoshi
authors: S
authors: Ishii
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D004789:Enzyme Activation; D000795:Fabry Disease / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D005820:Genetic Testing; D006017:Glycolipids / Q000097:blood*; D006801:Humans; D007564:Japan; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000235:genetics / Q000628:therapy; D008297:Male; D008403:Mass Screening / Q000379:methods* / Q000592:standards; D008875:Middle Aged; D006435:Renal Dialysis; D015203:Reproducibility of Results; D013107:Sphingolipids / Q000097:blood*; D000519:alpha-Galactosidase / Q000097:blood / Q000235:genetics
chemical_list: D015415:Biomarkers; D006017:Glycolipids; D013107:Sphingolipids; C063288:globotriaosyl lysosphingolipid; D000519:alpha-Galactosidase