title: Reduction of elevated plasma globotriaosylsphingosine in patients with classic Fabry disease following enzyme replacement therapy.
abstract: Fabry disease is treated by two-weekly infusions with α-galactosidase A, which is deficient in this X-linked globotriaosylceramide (Gb3) storage disorder. Elevated plasma globotriaosylsphingosine (lysoGb3) is a hallmark of classical Fabry disease. We investigated effects of enzyme replacement therapy (ERT) on plasma levels of lysoGb3 and Gb3 in patients with classical Fabry disease treated with agalsidase alfa at 0.2mg/kg, agalsidase beta at 0.2mg/kg or at 1.0mg/kg bodyweight. Each treatment regimen led to prominent reductions of plasma lysoGb3 in Fabry males within 3 months (P=0.0313), followed by relative stability later on. Many males developed antibodies against α-galactosidase A, particularly those treated with agalsidase beta. Patients with antibodies tended towards smaller correction in plasma lysoGb3 concentration, whereas treatment with high dose agalsidase beta allowed a reduction comparable to patients without antibodies. Pre-treatment plasma lysoGb3 concentrations of Fabry females were relatively low. In all females and with each treatment regimen, ERT gave reduction or stabilisation of plasma lysoGb3. Our investigation revealed that ERT of Fabry patients reduces plasma lysoGb3, regardless of the recombinant enzyme used. This finding shows that ERT can correct a characteristic biochemical abnormality in Fabry patients.
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Mariëlle J
authors.initials: MJ
authors.lastname: van Breemen
authors.forename: Saskia M
authors.initials: SM
authors.lastname: Rombach
authors.forename: Nick
authors.initials: N
authors.lastname: Dekker
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Poorthuis
authors.forename: Gabor E
authors.initials: GE
authors.lastname: Linthorst
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: Frank
authors.initials: F
authors.lastname: Breunig
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Aerts
authors.forename: Carla E
authors.initials: CE
authors.lastname: Hollak
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D056947:Enzyme Replacement Therapy / Q000379:methods*; D000795:Fabry Disease / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006017:Glycolipids / Q000097:blood*; D006801:Humans; D007527:Isoenzymes / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D013107:Sphingolipids / Q000097:blood*; D016896:Treatment Outcome; D055815:Young Adult; D000519:alpha-Galactosidase / Q000276:immunology / Q000627:therapeutic use
chemical_list: D000906:Antibodies; D006017:Glycolipids; D007527:Isoenzymes; D008055:Lipids; D011994:Recombinant Proteins; D013107:Sphingolipids; C063288:globotriaosyl lysosphingolipid; C000627036:agalsidase alfa; D000519:alpha-Galactosidase; C459420:agalsidase beta