Correlations between Endomyocardial Biopsies and Cardiac Manifestations in Taiwanese Patients with the Chinese Hotspot IVS4+919G>A Mutation: Data from the Fabry Outcome Survey

Int J Mol Sci. 2017 Jan 9;18(1):119. doi: 10.3390/ijms18010119.

Abstract

We retrospectively evaluated correlations between cardiac manifestations and globotriaosylceramide (Gb3) accumulation in cardiomyocytes from Taiwanese patients with Fabry disease and the IVS4+919G>A (IVS4) mutation who underwent endomyocardial biopsy (Shire; Fabry Outcome Survey data; extracted January 2015). Of 24 males and six females (median age [Q1; Q3] at biopsy 60.4 [57.4; 64.1] and 61.3 [60.4; 65.1] years, respectively), 13 males (54.2%) and five females (83.3%) received agalsidase alfa enzyme replacement therapy (ERT) before biopsy. Median left ventricular mass indexed to height (LVMI) within ±6 months of biopsy was 65.3 (52.7; 93.1) in males and 53.2 (42.0; 55.0) g/m2.7 in females. A moderate, positive, statistically significant correlation was found between the percentage area Gb3 accumulation in cardiomyocytes and LVMI (Spearman's ρ, 0.45; p = 0.014); a smaller, positive, non-statistically significant correlation was observed between cardiomyocyte diameter and LVMI (Spearman's ρ 0.16, p = 0.394). Moderate, statistically significant, negative correlations were found between Gb3 accumulation and ERT duration (Spearman's ρ, -0.49, p = 0.007) and between cardiomyocyte size and ERT duration (Spearman's ρ, -0.37, p = 0.048). Longer ERT duration was associated with smaller amounts of Gb3 accumulation and smaller cardiomyocyte size. Further follow-up is recommended to confirm these trends in a larger sample size.

Keywords: Fabry Outcome Survey; Fabry disease; endomyocardial biopsy; enzyme replacement therapy; hypertrophic cardiomyopathy.

MeSH terms

  • Biopsy
  • Demography
  • Fabry Disease / genetics*
  • Fabry Disease / pathology*
  • Female
  • Health Surveys*
  • Heart Ventricles
  • Humans
  • Image Processing, Computer-Assisted
  • Kidney / pathology
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Myocardium / pathology*
  • Myocytes, Cardiac / pathology
  • Organ Size
  • Software
  • Taiwan
  • Treatment Outcome
  • Trihexosylceramides / metabolism

Substances

  • Trihexosylceramides
  • globotriaosylceramide