A pilot study of discontinuous, insulin-like growth factor 1-dosing growth hormone treatment in young children with FGFR3 N540K-mutated hypochondroplasia

J Pediatr. 2012 May;160(5):849-53. doi: 10.1016/j.jpeds.2011.10.023. Epub 2011 Dec 2.

Abstract

Objective: To assess the growth promoting effect of a recombinant growth hormone (rGH) treatment protocol adjusted on insulin-like growth factor 1 (IGF-1) dosing in children affected by the most severe forms of FGFR3 N540K-mutated hypochondroplasia.

Study design: Midterm results of an open-label, single-center, nonrandomized, 2003-2020 pilot trial to final stature, including 6 children (mean age, 2.6 ± 0.7 years; mean height SDS, -3.0 ± 0.5) with the N540K mutation of FGFR3 gene who received an rGH dosage titrated to an IGF-1 level close to 1.5 SDS of the normal range. rGH therapy was interrupted 1 day per week, 1 month per year, and 6 months every 2 years.

Results: The mean height SDS increased by 1.9 during the 6.1 ± 0.9-year study period, reaching -0.8 to -1.3 at age 8.7 ± 1 years. The mean±SDS baseline IGF-1 value was -1.6 ± 0.5 before rGH treatment and 1.4±0.3 during the last year of observation. The average cumulative rGH dose was 0.075 ± 0.018 mg/kg/day (range, 0.059-0.100 mg/kg/day). Trunk/leg disproportion was improved.

Conclusion: IGF-1-dosing rGH treatment durably improves growth and reduces body disproportion in children with severe forms of hypochondroplasia.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Body Height / drug effects
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Dwarfism / drug therapy*
  • Dwarfism / genetics*
  • Female
  • Follow-Up Studies
  • France
  • Human Growth Hormone / administration & dosage*
  • Humans
  • Insulin-Like Growth Factor I / drug effects
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Mutation
  • Osteochondrodysplasias / diagnosis
  • Osteochondrodysplasias / drug therapy*
  • Osteochondrodysplasias / genetics
  • Pilot Projects
  • Rare Diseases
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics*
  • Receptor, Fibroblast Growth Factor, Type 3 / metabolism
  • Risk Assessment
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome

Substances

  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3