Abstract | OBJECTIVE: STUDY DESIGN: Fourteen male and 2 female patients, 8 to 16 years old, were treated in this open-label study. A 12-week observation period to collect baseline data preceded the 48-week treatment period when agalsidase beta (1 mg/kg) was infused intravenously every 2 weeks. No primary efficacy end point was specified. RESULTS: Before treatment, results of skin biopsies from 12 male patients showed moderate or severe GL-3 accumulation in superficial dermal capillary endothelial cells; with treatment, these cells were completely cleared of GL-3 in week-24 biopsies from all 12 male patients and in all available week-48 biopsies. With treatment, reports of gastrointestinal symptoms declined steadily. Patient diaries documented significant reductions in school absences due to sickness. Agalsidase beta was generally well tolerated; most treatment-related adverse events were mild or moderate infusion-associated reactions involving rigors, fever, or rhinitis. CONCLUSIONS:
Agalsidase beta safely and effectively reduced the GL-3 accumulation in dermal endothelium already evident in children with Fabry disease. Early intervention may prevent irreversible end-organ damage from chronic GL-3 deposition.
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Authors | J Edmond Wraith, Anna Tylki-Szymanska, Nathalie Guffon, Y Howard Lien, Michel Tsimaratos, Ashok Vellodi, Dominique P Germain |
Journal | The Journal of pediatrics
(J Pediatr)
Vol. 152
Issue 4
Pg. 563-70, 570.e1
(Apr 2008)
ISSN: 1097-6833 [Electronic] United States |
PMID | 18346516
(Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies
- Immunoglobulin G
- Isoenzymes
- Trihexosylceramides
- globotriaosylceramide
- Creatinine
- alpha-Galactosidase
- agalsidase beta
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Topics |
- Adolescent
- Antibodies
(blood)
- Capillaries
(metabolism)
- Child
- Creatinine
(blood)
- Dermis
(blood supply, metabolism)
- Endothelium
(metabolism)
- Fabry Disease
(blood, drug therapy, physiopathology)
- Female
- Growth
- Humans
- Immunoglobulin G
(blood)
- Infusions, Intravenous
- Isoenzymes
(adverse effects, immunology, therapeutic use)
- Male
- Nausea
- Trihexosylceramides
(metabolism)
- alpha-Galactosidase
(adverse effects, immunology, therapeutic use)
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