title: Correlations between Endomyocardial Biopsies and Cardiac Manifestations in Taiwanese Patients with the Chinese Hotspot IVS4+919G>A Mutation: Data from the Fabry Outcome Survey.
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/m2.7in 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.
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei 112, Taiwan. romberg@gmail.com.|Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan. romberg@gmail.com.
authors.forename: Ting-Rong
authors.initials: TR
authors.lastname: Hsu
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan. orimiltea@gmail.com.|Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan. orimiltea@gmail.com.
authors.forename: Fu-Pang
authors.initials: FP
authors.lastname: Chang
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei 112, Taiwan. mno4.chu@gmail.com.
authors.forename: Tzu-Hung
authors.initials: TH
authors.lastname: Chu
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University, Taipei 112, Taiwan. shsang@vghtpe.gov.tw.
authors.forename: Shih-Hsien
authors.initials: SH
authors.lastname: Sung
authors.affiliation: Shire, 6300 Zug, Switzerland. sbizjajeva@shire.com.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Bizjajeva
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University, Taipei 112, Taiwan. wcyu@vghtpe.gov.tw.
authors.forename: Wen-Chung
authors.initials: WC
authors.lastname: Yu
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei 112, Taiwan. dmniu1111@yahoo.com.tw.|Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan. dmniu1111@yahoo.com.tw.
authors.forename: Dau-Ming
authors.initials: DM
authors.lastname: Niu
mesh_terms: D001706:Biopsy; D003710:Demography; D000795:Fabry Disease / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006306:Health Surveys; D006352:Heart Ventricles; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007668:Kidney / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D009929:Organ Size; D012984:Software; D013624:Taiwan; D016896:Treatment Outcome; D014281:Trihexosylceramides / Q000378:metabolism
chemical_list: D014281:Trihexosylceramides; C018549:globotriaosylceramide
keywords: Fabry Outcome Survey; Fabry disease; endomyocardial biopsy; enzyme replacement therapy; hypertrophic cardiomyopathy