Treatment with recombinant human insulin-like growth factor-1 improves growth in patients with PAPP-A2 deficiency

María Teresa Muñoz-Calvo, Vicente Barrios, Jesús Pozo, Julie A Chowen, Gabriel Á Martos-Moreno, Federico Hawkins, Andrew Dauber, Horacio M Domené, Shoshana Yakar, Ron G Rosenfeld, Luis A Pérez-Jurado, Claus Oxvig, Jan Frystyk, Jesús Argente

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40 Citations (Scopus)

Abstract

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 mu;g/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. (J Clin Endocrinol Metab 101: 3879-3883, 2016).

Original languageEnglish
JournalThe Journal of Clinical Endocrinology & Metabolism
Volume101
Issue11
Pages (from-to)3879-3883
Number of pages5
ISSN0021-972X
DOIs
Publication statusPublished - Nov 2016

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