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

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

Research output: Contribution to journalArticlepeer-review


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 (US)
Pages (from-to)3879-3883
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Issue number11
StatePublished - Nov 2016

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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