Recombinant human IGF-I was first available for experimental therapy in the late 1980s, what allowed the development of long-term studies in children with severe primary IGF-I deficiency (defined as a height SDS and IGF-I SDS less than or equal to −3 and normal or elevated GH levels)[375]. The gene discussed is GH1; the disease is hyperinsulinemic hypoglycemia, familial, 4.