The effect of enzyme replacement therapy on clinical outcomes in paediatric patients with Fabry disease - A systematic literature review by a European panel of experts

Mol Genet Metab. 2019 Mar;126(3):212-223. doi: 10.1016/j.ymgme.2018.04.007. Epub 2018 Apr 26.

Abstract

Background: Fabry disease is caused by a deficiency of the lysosomal enzyme α-galactosidase, resulting in progressive accumulation of globotriaosylceramide (GL-3). The disease can manifest early during childhood and adolescence. Enzyme replacement therapy (ERT) with recombinant human α-galactosidase is the first specific treatment for Fabry disease and has been available in Europe since 2001. This paper presents the findings of a systematic literature review of clinical outcomes with ERT in paediatric patients with Fabry disease.

Methods: A comprehensive systematic review of published literature on ERT in Fabry disease was conducted in January 2017. The literature analysis included all original articles reporting outcomes of ERT in paediatric patients.

Results: Treatment-related outcomes in the paediatric population were reported in six publications derived from open-label clinical trials and in 10 publications derived from observational or registry-based studies. ERT was shown to significantly reduce plasma and urine GL-3 levels in paediatric patients with Fabry disease. The effect of ERT on GL-3 clearance from renal podocytes appeared to be agalsidase dose-dependent. ERT relieved pain and improved gastrointestinal symptoms and quality of life.

Conclusions: Based on the published literature, the use of ERT in paediatric patients can significantly clear GL-3 accumulation, ameliorate the early symptoms of Fabry disease, and improve quality of life. Treatment with ERT in paediatric patients with Fabry disease may be important to prevent further disease progression and overt organ damage.

Keywords: Agalsidase alfa; Agalsidase beta; Enzyme replacement therapy; Fabry disease; Paediatric patients; Systematic literature review.

Publication types

  • Systematic Review

MeSH terms

  • Child
  • Enzyme Replacement Therapy*
  • Europe
  • Fabry Disease / therapy*
  • Female
  • Humans
  • Isoenzymes / therapeutic use
  • Male
  • Observational Studies as Topic
  • Pain / drug therapy
  • Quality of Life
  • Randomized Controlled Trials as Topic
  • Recombinant Proteins / therapeutic use
  • Treatment Outcome
  • Trihexosylceramides / metabolism
  • alpha-Galactosidase / therapeutic use

Substances

  • Isoenzymes
  • Recombinant Proteins
  • Trihexosylceramides
  • agalsidase alfa
  • globotriaosylceramide
  • alpha-Galactosidase
  • agalsidase beta