title: Surges in proteinuria are associated with plasma GL-3 elevations in a young patient with classic Fabry disease.
abstract: Fabry disease is an X-linked glycosphingolipidosis caused by deficient synthesis of the enzyme α-galactosidase A, which results in accumulations of globotriaosylceramide (GL-3) in systemic tissues. Nephropathy is a dominant feature of Fabry disease. It still remains unclear how the nephropathy progresses. Recombinant agalsidase replacement therapy is currently the only approved, specific therapy for Fabry disease. The optimal dose of replacement enzyme also still remains unclear. The worldwide shortage of agalsidase-β in 2009 forced dose reduction of administration. It showed that the proteinuria emerged like surges, followed by temporary plasma GL-3 elevations in the early stages of classic Fabry disease. Additionally, it also showed that 1 mg/kg of agalsidase-β every other week could clear the GL-3 accumulations from podocytes and was required to maintain negative proteinuria and normal plasma GL-3 levels.
  
  
  CONCLUSIONS
  This observation of a young patient with classic Fabry disease about 5 years reveals that the long-term, low-dose agalsidase-β caused proteinuria surges, but not persistent proteinuria, followed by temporary plasma GL-3 elevations, and agalsidase-β at 1 mg/kg every other week could clear accumulated GL-3 from podocytes and was required to maintain normal urinalysis and plasma GL-3 levels.
authors.affiliation: Department of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan. tkanai@jichi.ac.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kanai
authors.affiliation: Department of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan. takane@jichi.ac.jp.
authors.forename: Takane
authors.initials: T
authors.lastname: Ito
authors.affiliation: Department of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan. mrjo@jichi.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Odaka
authors.affiliation: Department of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan. tk-sait@jichi.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan. r-jun-mem@jichi.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Aoyagi
authors.affiliation: Department of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan. bettsu@jichi.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Betsui
authors.affiliation: Department of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan. takanori@jichi.ac.jp.
authors.forename: Takanori
authors.initials: T
authors.lastname: Yamagata
mesh_terms: D000293:Adolescent; D056947:Enzyme Replacement Therapy / Q000379:methods; D000795:Fabry Disease / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D007527:Isoenzymes / Q000008:administration & dosage*; D007674:Kidney Diseases / Q000150:complications; D008297:Male; D050199:Podocytes / Q000473:pathology*; D011507:Proteinuria / Q000097:blood*; D014281:Trihexosylceramides / Q000097:blood*; D000519:alpha-Galactosidase / Q000008:administration & dosage*
chemical_list: D007527:Isoenzymes; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D000519:alpha-Galactosidase; C459420:agalsidase beta
keywords: Enzyme replacement therapy; Fabry disease; Foot process effacement; Podocyte; Proteinuria; Renal pathology