title: Long-term enzyme replacement therapy for Fabry disease: efficacy and unmet needs in cardiac and renal outcomes.
abstract: Fabry disease is a progressive lysosomal storage disease caused by alpha-galactosidase A deficiency. This condition is characterized by progressive accumulation of glycosphingolipids with functional impairment in various organs, including the kidney, heart and cerebrovascular system. Enzyme replacement therapy (ERT) is essential because it attenuates the disease progression. The present study investigated the long-term efficacy of ERT in 19 Korean Fabry patients (11 adult males, 4 symptomatic female carriers and 4 pediatric males) who had received ERT for 8.1±2.2 years (range, 5.3-10.5 years). In the 11 adult males, the mean reduction in the estimated glomerular filtration rate (eGFR) was -3.8±4.5 ml-1min 1.73 m-2. The rate of eGFR decline was significantly lower in patients with lower proteinuria (<1 g per day) before ERT. The left ventricular mass index decreased or was stable throughout the ERT in male patients with or without left ventricular hypertrophy before ERT initiation. In female carriers and pediatric male patients, renal and cardiac functions remained stable with ERT. Arrhythmias were observed in 10 adult males and 1 female patient before ERT and persisted during ERT. One pediatric patient newly developed arrhythmia despite ERT. In conclusion, long-term ERT has beneficial effects on the renal and cardiac outcomes of Fabry patients but has limited effect in patients with irreversible organ damage. Identification of patients in the early disease stage and rapid ERT initiation might be the best strategy to improve the natural course of the disease.
authors.affiliation: Department of Pediatrics, Hanyang University College of Medicine, Hanyang University Guri Hospital, Guri-si, Korea.
authors.forename: Ja Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.|Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Beom Hee
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Ja
authors.initials: J
authors.lastname: Hyang Cho
authors.affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Eungu
authors.initials: E
authors.lastname: Kang
authors.affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Gu-Hwan
authors.initials: GH
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.|Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Han-Wook
authors.initials: HW
authors.lastname: Yoo
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006331:Heart Diseases / Q000175:diagnosis / Q000209:etiology; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis / Q000209:etiology; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016896:Treatment Outcome; D055815:Young Adult; D000519:alpha-Galactosidase / Q000235:genetics / Q000627:therapeutic use*
chemical_list: D000519:alpha-Galactosidase