Plasma Globotriaosylsphingosine Level as a Primary Screening Target for Fabry Disease in Patients With Left Ventricular Hypertrophy

Circ J. 2019 Aug 23;83(9):1901-1907. doi: 10.1253/circj.CJ-19-0110. Epub 2019 Jul 12.


Background: Although previous studies have suggested a certain prevalence of Fabry disease (FD) in left ventricular hypertrophy (LVH) patients, the screening of FD is difficult because of its wide-ranging clinical phenotypes. We aimed to clarify the utility of combined measurement of plasma globotriaosylsphingosine (lyso-Gb3) concentration and α-galactosidase A activity (α-GAL) as a primary screening of FD in unexplained LVH patients.Methods and Results:Between 2014 and 2016, both lyso-Gb3 and α-GAL were measured in 277 consecutive patients (male 215, female 62, age 25-79 years) with left ventricular wall thickness >12 mm on echocardiogram: 5 patients (1.8%) screened positive (2 (0.7%) showed high lyso-Gb3 and 4 (1.4%) had low α-GAL levels). Finally, 2 patients (0.7%) were diagnosed with clinically significant FD. In 1 case, a female heterozygote with normal α-GAL levels had genetic variants of unknown significance and was diagnosed as FD by endomyocardial biopsy. The other case was a male chronic renal failure patient requiring hemodialysis, and he had a p.R112H mutation. In both cases there were high lyso-Gb3 levels.

Conclusions: The serum lyso-Gb3 level can be relevant for clinically significant FD, and combined measurement of lyso-Gb3 and α-GAL can provide better screening of FD in unexplained LVH patients.

Keywords: Fabry disease; Left ventricular hypertrophy; Lyso-Gb3; Primary screening; α-galactosidase A.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Fabry Disease / blood*
  • Fabry Disease / diagnostic imaging
  • Fabry Disease / genetics
  • Fabry Disease / physiopathology
  • Female
  • Genetic Predisposition to Disease
  • Glycolipids / blood*
  • Humans
  • Hypertrophy, Left Ventricular / blood*
  • Hypertrophy, Left Ventricular / diagnostic imaging
  • Hypertrophy, Left Ventricular / genetics
  • Hypertrophy, Left Ventricular / physiopathology
  • Japan
  • Male
  • Middle Aged
  • Mutation
  • Predictive Value of Tests
  • Prospective Studies
  • Sphingolipids / blood*
  • Ventricular Function, Left
  • Ventricular Remodeling
  • Young Adult
  • alpha-Galactosidase / blood
  • alpha-Galactosidase / genetics


  • Biomarkers
  • Glycolipids
  • Sphingolipids
  • globotriaosyl lysosphingolipid
  • GLA protein, human
  • alpha-Galactosidase

Supplementary concepts

  • Fabry Disease, Cardiac Variant