PAPP-A2 a new key regulator of growth

Endokrynol Pol. 2017;68(6):682-691. doi: 10.5603/EP.a2017.0060.


Short stature is the main problem that paediatric endocrinologists have to grapple with. Endocrine disorders account for only 5% of patients with short stature, but this is still one of the most common causes of reports to the endocrine clinic and hospitalisation in the endocrine department. A properly functioning growth hormone/insulin-like growth factor (GH/IGF) axis is one of the most important factors in proper growth. A lot of genetic defects in this axis lead to syndromes marked by impaired growth, like Laron syndrome, muta-tions in the STAT5B, insulin-like growth factor 1 (IGF1), and insulin-like growth factor 1 receptor (IGF1R) and mutations in the acid labile subunit (ALS). Two proteases important for the proper functioning of the GH/IGF axis: pregnancy-associated plasma protein-A (PAPP-A) and pregnancy-associated plasma protein-A2 (PAPP-A2), have been described. The first description of the new syndrome of growth failure associated with mutation in the PAPP-A2 gene was given by Andrew Dauber et al. This review evaluates the current data concerning PAPP-A2 function, and particularly the effect of PAPP-A2 mutation on growth.

Keywords: GH; IGF1; PAPP-A2; growth; short stature.

Publication types

  • Review

MeSH terms

  • Animals
  • Female
  • Growth / genetics*
  • Growth Hormone
  • Humans
  • Insulin-Like Growth Factor I
  • Male
  • Mice
  • Mutation*
  • Pregnancy-Associated Plasma Protein-A / metabolism
  • Pregnancy-Associated Plasma Protein-A / physiology*


  • Insulin-Like Growth Factor I
  • Growth Hormone
  • PAPPA2 protein, human
  • PAPPA2 protein, mouse
  • Pregnancy-Associated Plasma Protein-A