重组人胰岛素样生长因子-1治疗可改善PAPP-A2缺乏症患者的生长情况。
Treatment With Recombinant Human Insulin-Like Growth Factor-1 Improves Growth in Patients With PAPP-A2 Deficiency.
作者信息
Muñoz-Calvo María T, Barrios Vicente, Pozo Jesús, Chowen Julie A, Martos-Moreno Gabriel Á, Hawkins Federico, Dauber Andrew, Domené Horacio M, Yakar Shoshana, Rosenfeld Ron G, Pérez-Jurado Luis A, Oxvig Claus, Frystyk Jan, Argente Jesús
机构信息
Department of Pediatrics and Pediatric Endocrinology (M.T.M.-C., V.B., J.P., J.A.C., G.A.M.-M., J.A.) Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Universidad Autónoma de Madrid, Department of Pediatrics, Centro de Investigación Biomédica en Red (CIBEROBN), Instituto de Salud Carlos III, 28009 Madrid, Spain; Department of Endocrinology (F.H.), Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, 28040 Madrid, Spain; Cincinnati Center for Growth Disorders (A.D.), Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE) (H.M.D.), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), FEI, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina; Department of Basic Science and Craniofacial Biology (S.Y.), New York University College of Dentistry, New York, New York 10010; Oregon Health and Science University (R.G.R.), Portland, Oregon 97239; Stat5 LLC (R.G.R.), Los Altos, California 94022; Genetics Unit (L.A.P.-J.), Universitat Pompeu Fabra, Hospital del Mar Research Institute (IMIM), and CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08003 Barcelona, Spain; Department of Molecular Biology and Genetics (C.O.), Aarhus University, 8000 Aarhus, Denmark; and Medical Research Laboratory (J.F.), Department of Clinical Medicine, Faculty of Health, Aarhus University and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
出版信息
J Clin Endocrinol Metab. 2016 Nov;101(11):3879-3883. doi: 10.1210/jc.2016-2751. Epub 2016 Sep 20.
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 μg/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.
背景
妊娠相关血浆蛋白-A2（PAPP-A2）是一种金属蛋白酶，可特异性切割胰岛素样生长因子结合蛋白-3（IGFBP-3）和胰岛素样生长因子结合蛋白-5（IGFBP-5）。最近研究表明，PAPP-A2基因突变会导致人类出生后生长发育迟缓，并伴有特定的骨骼特征，这是由于IGF-1生物利用度降低所致。然而，针对该疾病的药物治疗方法尚未确立。
病例描述
一名10.5岁女孩和一名6岁男孩为西班牙家庭的兄妹，因PAPP-A2基因纯合功能缺失突变（p.D643fs25*）导致身材矮小，且PAPP-A2活性检测不到。他们每天两次接受递增剂量（40、80、100和120μg/kg）的重组人生长激素（rhIGF-1）治疗，持续1年。兄妹俩的生长速度和身高均明显增加。急性给予rhIGF-1后，生物活性IGF-1增加，自发性生长激素分泌减少，而血清总IGF-1和IGFBP-3水平仍保持升高。治疗期间未观察到低血糖发作或任何其他副作用。
结论
rhIGF-1短期治疗可改善PAPP-A2缺乏患者的生长情况。
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