Enzyme replacement therapy for Gaucher disease in Australia

Intern Med J. 2005 Mar;35(3):156-61. doi: 10.1111/j.1445-5994.2004.00765.x.

Abstract

Aim: To study the effectiveness of a specific national programme of enzyme replacement therapy (ERT) for patients with severe forms of Gaucher disease, a disorder of sphingolipid metabolism resulting from an inherited deficiency of the lysosomal enzyme beta-Glucocerebrosidase.

Methods: Prospective analysis of data submitted at entry and every 6 months on therapy. The responses of haemoglobin (Hb) and platelet (plt) concentrations, liver and spleen volumes were assessed.

Patients: Forty-eight patients were treated with ERT for a minimum of 6 months. Forty patients had Type 1 disease and eight had Type 3B. The age range was 1-70 years (median 24 years). Duration of therapy at the time of analysis was 6-114 months.

Results: Thirty-six per cent of patients started with a normal Hb increasing to 76% after 6 months. The mean improvement in Hb from baseline to the end of study period was 20 g/L, when the Hb was normal in 85% (41 patients). Thirty per cent of patients had a normal plt count at the start of therapy, with a more gradual increase in the count at 6 monthly intervals of 50, 91, 108 and 142% of starting value. Seventy-five per cent of patients had a normal plt count at the end of study. Spleen volumes reduced by a mean of 56% in 33 evaluable patients, and the liver by 27% in 30 of 38 evaluable patients. Eight patients had an increase in liver volume of 28%.

Conclusion: Enzyme replacement therapy produced a spectrum of beneficial responses in patients with Gaucher disease, but all had some evidence of reversal of haematological complications and/or reduction in visceromegaly. Future analyses will examine the effect of therapy on bone disease, prepubertal growth and quality of life.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Cells / enzymology
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Fibroblasts / enzymology
  • Follow-Up Studies
  • Gaucher Disease / blood
  • Gaucher Disease / drug therapy*
  • Gaucher Disease / genetics
  • Genotype
  • Glucosylceramidase / administration & dosage
  • Glucosylceramidase / genetics
  • Glucosylceramidase / metabolism
  • Glucosylceramidase / therapeutic use*
  • Hemoglobins / metabolism
  • Humans
  • Infant
  • Infusions, Intravenous
  • Liver / diagnostic imaging
  • Liver / pathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation
  • Platelet Count
  • Prospective Studies
  • Spleen / diagnostic imaging
  • Spleen / pathology
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Hemoglobins
  • alglucerase
  • Glucosylceramidase
  • imiglucerase