Growth hormone insensitivity syndrome (GHIS) of genetic origin is associated with many different mutations of the growth hormone receptor (GHR) gene and a recently described genetic defect of the insulin-like growth factor I (IGF-I) gene.
Growth hormone insensitivity syndrome (GHIS), a genetic disease characterized by growth retardation combined with high serum concentration of growth hormone (GH) and low insulin-like growth factor 1 (IGF-1) levels, can be caused by mutations in the GH receptor (GHR) gene.
Growth hormone receptor deficiency (GHRD) results in short stature, enhanced insulin sensitivity, and low circulating levels of insulin and insulin-like growth factor 1 (IGF-1).
Laron-type dwarfism is an autosomal recessive genetic disorder that is characterized by high levels of growth hormone and low levels of insulin-like growth factor I in the circulation.
Laron syndrome (LS) is a genetic type of dwarfism that results from mutation of the growth hormone receptor (<i>GHR</i>) gene, and is the best characterized entity under the spectrum of the congenital IGF1 deficiencies.
Insulin-like growth factor-I and insulin-like growth factor binding protein-3 cotreatment versus insulin-like growth factor-I alone in two brothers with growth hormone insensitivity syndrome: effects on insulin sensitivity, body composition and linear growth.
As all patients with LS are IGF-I-deficient, it must be assumed that other as yet unknown factors related to the molecular defects in the GH-R are the major cause of the differences in intellect and brain abnormalities.
Classic Laron Syndrome (LS) is a recessive disease of insulin-like growth factor I (IGF-I) deficiency and primary growth hormone insensitivity, clinically characterized by dwarfism and marked obesity.
Clinical and laboratory investigations starting in 1958 of a group of dwarfed children resembling isolated GH deficiency but who had very high serum levels of GH led to the description of the syndrome of primary GH resistance or insensitivity (Laron syndrome) and subsequently to the discovery of its molecular defects residing in the GH receptor and leading to an inability of IGF-I generation.
Clinical investigations started in 1958 of a group of children with characteristics resembling GH deficiency, but who had extremely high levels of plasma GH, led to the description of the syndrome of primary GH resistance or insensitivity (Laron syndrome), the discovery of its molecular defect, and the clinical application of biosynthetic insulin-like growth factor-I.
Conclusions Sequential measurements of serum IGF-I, glucose and potassium in patients with Laron syndrome may aid in optimizing and individualizing rhIGF-I treatment.
Expression of heterozygosity for the defect in the growth hormone (GH) receptor has been proposed to be reflected in stature, and in GH binding protein (GHBP) and insulin-like growth factor I (IGF-I) levels in parents and other relatives of patients with GH receptor deficiency (GHRD; Laron syndrome).
GH insensitivity syndrome (GHIS; Laron syndrome) is clinically characterized by severe postnatal growth failure and very low serum levels of IGF-I despite increased secretion of GH.
GH-dependent IGF-I and IGFBP-3 secretion is not affected by heterozygosity for the E180 splice mutation that causes GHRD/Laron syndrome in the Ecuadorian population.
In this study, we found that erythroid progenitor cells and permanently transformed T-cell lines from two patients with Laron dwarfism responded in vitro to added IGF-I in concentrations ranging between 1-10 ng/mL despite no stimulatory response to added GH in concentrations of up to 500 ng/mL.
It combines with insulin-like growth factor-I (IGF-I) to form a complex (IGF-I/IGFBP-3) that can treat growth hormone insensitivity syndrome (GHIS) and reduce insulin requirement in patients with diabetes.
It seems that the IGF-I-IGFBP-3 combination has a longer half-life in patients with GHIS than unbound IGF-I, with fewer reports of adverse events (including hypoglycaemia) when administered to patients with diabetes.
Most of the syndromes respond well to therapy with recombinant GH; exceptions are antibody-mediated resistance in GHD type IA (not all patients) and cases of Laron syndrome (GHR deficiency).Such patients respond to IGF-I therapy.
Mutations or deletions in the growth hormone receptor cause an autosomal disorder called Laron-type dwarfism (LS) characterized by high circulating levels of serum GH and low levels of insulin like growth factor-1 (IGF-1).
Patients present with short stature associated with high GH and low IGF-I levels and may have midfacial hypoplasia (typical Laron syndrome facial features).