title: Monitoring the clinical and biochemical response to enzyme replacement therapy in three children with Fabry disease.
abstract: Fabry disease is an X-linked disorder of glycosphingolipid metabolism resulting from a deficiency of the lysosomal enzyme alpha-galactosidase A. This leads to the progressive accumulation of glycosphingolipids in lysosomes of most visceral tissues and in body fluids. Following successful clinical trials in adults, two recombinant enzyme preparations of alpha-galactosidase have recently been licensed in Europe for the treatment of Fabry disease and treatment in children has commenced. We now report the clinical findings and the levels of globotriaosylceramide in plasma and urine in three boys who have been treated with enzyme replacement therapy (agalsidase beta, Fabrazyme), 1 mg/kg for 2 years. In one boy there was a rapid improvement in all the clinical and biochemical parameters measured. This has been maintained. In the other two boys, who are siblings, there was no measurable clinical improvement after 1 year and the levels of globotriaosylceramide in plasma and urine, although lower than before treatment, were still considerably elevated. There was no evidence of blocking or neutralising antibodies so the dose of enzyme was increased to 2 mg/kg at 74 weeks of therapy. At 2 years their pain scores had improved but this was not accompanied by any reduction in the plasma or urine globotriaosylceramide levels.
  
  
  CONCLUSIONS
  Measurement of globotriaosylceramide in plasma and urine may not be the most appropriate marker to monitor the progression of treatment by enzyme replacement therapy in all patients. Certainly the subjective clinical improvement in the two brothers in this report outweighed the objective biochemical findings.
authors.affiliation: Biochemistry, Endocrinology and Metabolism Unit, Institute of Child Health, University College London, 30 Guilford Street, WC1N 1EH London, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Mills
authors.forename: Ashok
authors.initials: A
authors.lastname: Vellodi
authors.forename: Peter
authors.initials: P
authors.lastname: Morris
authors.forename: Donald
authors.initials: D
authors.lastname: Cooper
authors.forename: Michael
authors.initials: M
authors.lastname: Morris
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Young
authors.forename: Bryan
authors.initials: B
authors.lastname: Winchester
mesh_terms: D002849:Chromatography, Gas; D000795:Fabry Disease / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000627:therapeutic use*; D008297:Male; D008991:Monitoring, Physiologic; D009154:Mutation; D021241:Spectrometry, Mass, Electrospray Ionization; D016896:Treatment Outcome; D014281:Trihexosylceramides / Q000097:blood / Q000378:metabolism* / Q000652:urine; D000519:alpha-Galactosidase / Q000235:genetics / Q000627:therapeutic use*
chemical_list: D007527:Isoenzymes; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D000519:alpha-Galactosidase; C459420:agalsidase beta