肢端短小症 FGFR3 N540K 突变患儿间断、胰岛素样生长因子 1 剂量生长激素治疗的初步研究。

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

机构信息

Service d'Endocrinologie Pédiatrique, Hôpitaux Universitaires Paris Sud, Paris, France.

出版信息

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

DOI:10.1016/j.jpeds.2011.10.023

PMID:22137367

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.

摘要

目的

评估根据胰岛素样生长因子 1（IGF-1）剂量调整重组生长激素（rGH）治疗方案对受 FGFR3 N540K 突变性成骨不全症最严重形式影响的儿童的生长促进作用。

研究设计

2003 年至 2020 年期间进行的一项开放标签、单中心、非随机、试点试验的中期结果，旨在最终身高，包括 6 名儿童（平均年龄 2.6 ± 0.7 岁；平均身高 SDS-3.0 ± 0.5），他们接受了 rGH 剂量滴定，以使 IGF-1 水平接近正常范围的 1.5 SDS。rGH 治疗每周中断 1 天，每年中断 1 个月，每 2 年中断 6 个月。

结果

在 6.1 ± 0.9 年的研究期间，平均身高 SDS 增加了 1.9，在 8.7 ± 1 岁时达到-0.8 至-1.3。rGH 治疗前平均±SDS 基线 IGF-1 值为-1.6 ± 0.5，最后一年观察时为 1.4±0.3。平均累积 rGH 剂量为 0.075 ± 0.018 mg/kg/天（范围 0.059-0.100 mg/kg/天）。躯干/下肢比例得到改善。