Treatment With Recombinant Human Insulin-Like Growth Factor-1 Improves Growth in Patients With PAPP-A2 Deficiency
Treatment With Recombinant Human Insulin-Like Growth Factor-1 Improves Growth in Patients With PAPP-A2 Deficiency
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DOI：
10.1210/jc.2016-2751
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发表时间：
2016-11-01
影响因子：
5.8
通讯作者：
Argente, Jesus
中科院分区：
文献类型：
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作者：
Munoz-Calvo, Maria T.;Barrios, Vicente;Argente, Jesus
背景：妊娠相关血浆蛋白-A2(PAPP-A2)是一种能特异性降解IGFBP-3和IGFBP-5的金属蛋白酶。由于IGF-1生物利用度的降低，PAPP-A2基因的突变最近被证明会导致人类出生后发育障碍，具有特定的骨骼特征。病例描述：一名10.5岁的女孩和一名6岁的男孩来自一个西班牙家庭，由于PAPP-A2基因(p.D643fs25*)的纯合子功能突变而导致身材矮小，并且无法检测到PAPP-A2活性，他们接受了渐进剂量(40、80、100和120头/公斤)的重组人IGF-1(rhIGF-1)的渐进剂量治疗，为期一年。两个兄弟姐妹的生长速度和身高都有明显的增加。急性应用重组人胰岛素样生长因子-1后，血清总IGF-1和IGFBP-3水平持续升高，生物活性IGF-1增加，GH自发分泌减少。治疗过程中未观察到低血糖或任何其他副作用。结论：短期应用重组人胰岛素样生长因子-1可改善PAPP-A2缺乏症患者的生长发育。
Context: Pregnancy-associated plasma protein-A2 (PAPP-A2) is a metalloproteinase that specifically cleaves IGFBP-3 and IGFBP-5. Mutations in the PAPP-A2 gene have recently been shown to cause postnatal growth failure in humans, with specific skeletal features, due to the resulting decrease in IGF-1 bioavailability. However, a pharmacological treatment of this entity is yet to be established.Case Description: A 10.5-year-old girl and a 6-year-old boy, siblings from a Spanish family, with short stature due to a homozygous loss-of-function mutation in the PAPP-A2 gene (p.D643fs25*) and undetectable PAPP-A2 activity, were treated with progressive doses (40, 80, 100, and 120 pig/kg) of recombinant human IGF-1 (rhIGF-1) twice daily for 1 year. There was a clear increase in growth velocity and height in both siblings. Bioactive IGF-1 was increased, and spontaneous GH secretion was diminished after acute administration of rhIGF-1, whereas serum total IGF-1 and IGFBP-3 levels remained elevated. No episodes of hypoglycemia or any other secondary effects were observed during treatment.Conclusion: Short-term treatment with rhIGF-1 improves growth in patients with PAPP-A2 deficiency.