PAPP-A2 deficiency is a novel syndrome characterized by short stature due to low IGF bioactivity, skeletal abnormalities and decreased bone mineral density (BMD). Treatment with recombinant human IGF-1 (rhIGF-1) for 1 year demonstrated to increase growth velocity and BMD, without reported adverse effects, but data regarding the long-term efficacy and safety of rhIGF-1 administration in this entity has not yet been reported.

Two Spanish siblings with short stature due to a homozygous loss-of-function mutation in the PAPP-A2 gene (p.D643fs25*) were treated with rhIGF-1 twice daily for six years. Growth velocity continued to increase and both patients achieved their target height. Free IGF-1 concentrations increased notably after rhIGF-1 administration, with serum IGFBP-3, IGFBP-5 and ALS levels also being higher during treatment. BMD was progressively normalized and an increase in lean mass was also noted during treatment. No episodes of hypoglycemia or any other adverse effects were documented. An increase in the growth of kidney and spleen length was observed in one of the patients.

PAPP-A2 缺乏症是一种新型综合征，其特征是由于 IGF 生物活性低、骨骼异常和骨矿物质密度 (BMD) 降低导致身材矮小。用重组人 IGF-1 (rhIGF-1) 治疗 1 年证明可增加生长速度和 BMD，但未报告不良反应，但有关 rhIGF-1 在该实体中长期疗效和安全性的数据尚未公布报道。

由于PAPP-A2基因 (p.D643fs25*) 中的纯合功能丧失突变导致身材矮小的两个西班牙兄弟姐妹每天两次接受 rhIGF-1 治疗，持续六年。生长速度继续增加，两名患者都达到了目标身高。rhIGF-1 给药后游离 IGF-1 浓度显着增加，治疗期间血清 IGFBP-3、IGFBP-5 和 ALS 水平也更高。BMD 逐渐正常化，并且在治疗期间也注意到瘦体重增加。没有记录到低血糖发作或任何其他不良反应。在其中一名患者中观察到肾脏和脾脏长度的增长。