TY - JOUR
T1 - Treatment with recombinant human insulin-like growth factor-1 improves growth in patients with PAPP-A2 deficiency
AU - Muñoz-Calvo, María T.
AU - Barrios, Vicente
AU - Pozo, Jesús
AU - Chowen, Julie A.
AU - Martos-Moreno, Gabriel
AU - Hawkins, Federico
AU - Dauber, Andrew
AU - Domené, Horacio M.
AU - Yakar, Shoshana
AU - Rosenfeld, Ron G.
AU - Pérez-Jurado, Luis A.
AU - Oxvig, Claus
AU - Frystyk, Jan
AU - Argente, Jesús
N1 - Publisher Copyright:
Copyright © 2016 by the Endocrine Society.
PY - 2016/11
Y1 - 2016/11
N2 - 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).
AB - 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).
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U2 - 10.1210/jc.2016-2751
DO - 10.1210/jc.2016-2751
M3 - Article
C2 - 27648969
AN - SCOPUS:84994876351
SN - 0021-972X
VL - 101
SP - 3879
EP - 3883
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 11
ER -