The impairments in glucose metabolism and bone mineral density described in patients with PAPP-A2 deficiency suggest that changes in signaling pathways of energy metabolism affected by insulin sensitivity and regulating bone development and remodeling in response to IGF1 treatment should be jointly evaluated as a key approach to better understand the physiological and metabolic derangements related to short stature. Here, PAPPA2 is linked to hyperinsulinemic hypoglycemia, familial, 4.