title: Foot process effacement is an early marker of nephropathy in young classic Fabry patients without albuminuria.
abstract: In Fabry disease, globotriaocylceramid (GL3) starts to accumulate in kidney cells in utero, and continues to accumulate throughout childhood and adulthood with progressive tissue damage, which may lead to renal failure.
  
  
  METHODS
  Eight children with classical Fabry disease, median age 12 (range 4-16 years) had a renal biopsy performed before the initiation of enzyme replacement therapy (ERT). All patients were normalbuminuric and had normal GFR. Three patients were re-biopsied after three or five years.
  
  
  RESULTS
  In all patients, significant GL3-accumulation was found in several types of kidney cells with high amounts of GL3 in the podocytes. Segmental podocyte foot process effacement was shown in all but two patients; no effacement was seen neither in the youngest male patient at 4 years of age nor in a male aged 12. A 12-year-old female patient had normal podocyte foot processes before the start of ERT, but de novo foot process flattening and unchanged high score of podocyte GL3 accumulation were seen in the re-biopsy after three years of ERT (agalsidase alpha 0.2 mg/kg/every other week). Two boys showed worsening of podocyte effacement in kidney biopsy after five years of agalsidase alpha 0.2 mg/kg/eow.
  
  
  CONCLUSIONS
  Podocyte foot process effacement was found in the majority of eight young classical Fabry patients of both genders after the age of 11 years, without clinical signs of Fabry nephropathy. Kidney biopsies are essential in the early diagnosis of nephropathy and in the evaluation of the response to enzyme replacement therapy of early Fabry nephropathy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Tøndel
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kanai
authors.forename: Kristin Kampevold
authors.initials: KK
authors.lastname: Larsen
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ito
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Politei
authors.forename: David G
authors.initials: DG
authors.lastname: Warnock
authors.forename: Einar
authors.initials: E
authors.lastname: Svarstad
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000419:Albuminuria / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D014281:Trihexosylceramides / Q000378:metabolism; D000519:alpha-Galactosidase / Q000235:genetics / Q000627:therapeutic use
chemical_list: D014281:Trihexosylceramides; C018549:globotriaosylceramide; D000519:alpha-Galactosidase