A 4-year study of the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa in 36 women with Fabry disease

Genet Med. 2009 Jun;11(6):441-9. doi: 10.1097/GIM.0b013e3181a23bec.


Purpose: Although Fabry disease is X linked and considered to affect primarily male hemizygotes, female heterozygotes may experience all the signs and symptoms of this metabolic disorder. This prospective, single-center, open-label, clinical trial was performed to evaluate the long-term response of female patients with Fabry disease to enzyme replacement therapy.

Methods: Symptomatic women (average age = 47 years) enrolled in this 4-year study were treated with agalsidase alfa (Replagal, Shire HGT, Inc.) at a dose of 0.2 mg/kg, every other week for 4 years (N = 36). Clinical and biochemical assessments were conducted at 12-month intervals.

Results: The Mainz Severity Score Index, a measure of total disease burden, was significantly reduced after 12 months (P < 0.01) of treatment and continuously improved over 4 years. Brief Pain Inventory "pain at its worst" score was reduced from 4.6 +/- 2.9 at baseline to 3.3 +/- 2.9 after 12 months (P = 0.001) and remained reduced through 4 years. Mean left-ventricular mass decreased from 89.4 +/- 29.3(2.7) g/m at baseline to 66.5 +/- 29.3(2.7) g/m after 12 months (P < 0.001) and remained reduced through 4 years. Average kidney function (estimated glomerular filtration rate and proteinuria) remained constant during the study. No safety issues were identified.

Conclusions: Long-term agalsidase alfa is effective and was well tolerated in women with Fabry disease.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Drug Administration Schedule
  • Fabry Disease / drug therapy*
  • Fabry Disease / genetics
  • Fabry Disease / pathology
  • Female
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Isoenzymes / therapeutic use
  • Leukocytes / enzymology
  • Middle Aged
  • Mutation
  • Prospective Studies
  • Recombinant Proteins
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult
  • alpha-Galactosidase / genetics
  • alpha-Galactosidase / metabolism
  • alpha-Galactosidase / therapeutic use*


  • Isoenzymes
  • Recombinant Proteins
  • agalsidase alfa
  • alpha-Galactosidase