title: Reaccumulation of globotriaosylceramide in podocytes after agalsidase dose reduction in young Fabry patients.
abstract: BACKGROUND
  Agalsidase-α 0.2 mg/kg every other week (eow) and agalsidase-β 1.0 mg/kg/eow are licensed in Europe as equipotent treatment of the α-galactosidase deficiency in Fabry disease. This case series describes the effects of agalsidase dose adjustments in serial kidney biopsies in switch patients.
  
  
  METHODS
  All treatment-naïve patients with classical Fabry disease in our centre started on agalsidase-β 1.0 mg/kg/eow and subsequently switched to agalsidase-α 0.2 mg/kg/eow were included ( n = 3). The median age at enzyme replacement therapy start was 11 (range 7-18) years. Kidney biopsies were performed at baseline, after 5 years of agalsidase-β 1.0 mg/kg/eow and after 3 subsequent years of agalsidase-α 0.2 mg/kg/eow. One patient was re-biopsied 2 years after reswitch to agalsidase-β 1.0 mg/kg/eow. The scoring system of the International Scoring Group of Fabry Nephropathy was used.
  
  
  RESULTS
  The patients completely cleared globotriaosylceramide (GL3) from mesangial and endothelial cells and partly cleared podocytes on agalsidase-β 1.0 mg/kg/eow. Reaccumulation of GL3 in podocytes, but not in the mesangium or endothelium, occurred after 3 years of agalsidase-α 0.2 mg/kg/eow. Subsequent reduction of podocyte GL3 was observed in the single patient rebiopsied 2 years after reswitch to agalsidase-β 1.0 mg/kg/eow.
  
  
  CONCLUSIONS
  Partial clearance, reaccumulation and renewed partial clearance of podocyte GL3 deposits in serial kidney biopsies over 8-10 years were seen in parallel with agalsidase dose adjustments. Repeated kidney biopsies may impact therapeutic choices in Fabry disease.
authors.affiliation: Department of Medicine, Haukeland University Hospital, Bergen, Norway.|Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Rannveig
authors.initials: R
authors.lastname: Skrunes
authors.affiliation: Department of Medicine, Haukeland University Hospital, Bergen, Norway.|Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Einar
authors.initials: E
authors.lastname: Svarstad
authors.affiliation: Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Kristin
authors.initials: K
authors.lastname: Kampevold Larsen
authors.affiliation: Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Sabine
authors.initials: S
authors.lastname: Leh
authors.affiliation: Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Camilla
authors.initials: C
authors.lastname: Tøndel
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D056947:Enzyme Replacement Therapy; D005060:Europe; D000795:Fabry Disease / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000008:administration & dosage; D008297:Male; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D014281:Trihexosylceramides / Q000378:metabolism*; D000519:alpha-Galactosidase / Q000008:administration & dosage*
chemical_list: D007527:Isoenzymes; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D000519:alpha-Galactosidase
keywords: Fabry disease; child; chronic kidney disease; histology; kidney biopsy