LARON SYNDROME DUE TO A POSTRECEPTOR DEFECT - RESPONSE TO IGF-I TREATMENT

Three siblings With Laron syndrome (LS) and normal serum growth hormon e binding protein (GHBP) are described. Basal serum levels of hGH were high and IGF-1 low, and in contradistinction to the classical form of the disease serum GHBP and IGFBP-3 were normal in these patients. Aft er 7 days of human growth hormone administration serum IGFBP-3 levels as well as the number of red blood cell IGF receptor sites increased. After short- and long-term IGF-1 administration the IGF-1 receptor bin ding capacity as well as the number of IGF receptor sites decreased to levels found in control subjects. One year treatment with IGF-1 incre ased the growth velocity by 47-96% in the two older children. It is co ncluded that the findings described are compatible with a normal GH re ceptor and normal signal transmission for IGFBP-3 synthesis but a defe ct exists in the post-GH receptor mechanism for the generation of IGF- 1. This is the first description of this type of defect leading to a v ariant of Laron syndrome.