Treatment with recombinant human insulin-like growth factor-I 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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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-I 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-I (rhIGF-I) twice daily for one year. There was a clear increase in growth velocity and height in both siblings. Bioactive IGF-I was increased and spontaneous GH secretion was diminished after acute administration of rhIGF-I, while serum total IGF-I 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-I improves growth in patients with PAPP-A2 deficiency.

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

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