The preservation of in vitro growth responsiveness to IGF-I in hematopoietic tissue from the Laron dwarfs suggests that affected individuals are sensitive to this factor and may respond to it in vivo.
We performed restriction enzyme analysis of the insulin-like growth factor I (IGF-I) gene on the families of 20 white British Caucasian children with short stature attributed to hypochondroplasia by radiological and clinical criteria, who were undergoing human growth hormone (r-hGH) treatment, in 60 children with isolated growth hormone deficiency and in 50 normal individuals.
This recessively transmitted hereditary disease, characterized clinically by dwarfism and obesity and biochemically by high levels of serum human growth hormone accompanied by low serum concentrations of insulin-like growth factor I, is diagnosed mainly in inbred societies of Asian Jews, Arabs, Iranians, Italians, and Spaniards or their descendants.
In GH-deficient dwarf rats (who have a primary GH deficiency), the excessive fat deposition induced by a high fat diet is completely reversed by combined infusion of GH and IGF-I.
To assess the clinical utility of growth-hormone-binding protein (GHBP), along with growth hormone (GH), insulin-like growth factor I (IGF-I), and insulin-like growth factor-binding protein 3 (IGFBP-3), levels in the evaluation of short stature.
The proband is a 3.5 year-old Druse girl with severe short stature (height SDS -5.1), high GH (250 micrograms/l), low IGF-I (2.7 nmol/l) and IGFBP-3 (410 micrograms/l), both unresponsive to exogenous GH.
We studied a 14 year-old girl with extreme short stature (-9.5 SDS), normal psychomotor development and signs of progressive hypothyroidism.Basal IGF-I and T4 were low.
We have recently reported a patient with a homozygous partial deletion of the insulin-like growth factor-I (IGF-I) gene, resulting in IGF-I deficiency, insulin resistance, and short stature.
Different forms of therapy, potassium and magnesium substitution, spironolactone and indomethacin failed to fully correct hypokalemia and hypomagnesemia, but markedly improved growth velocity and normalized IGF-I levels in the three patients with short stature.
Poor reproducibility of IGF-I and IGF binding protein-3 generation test in children with short stature and normal coding region of the GH receptor gene.
We thus tried to detect any mutation in the IGF-I gene that could be responsible for short stature in children, using PCR, single-strand conformation polymorphism (SSCP) analysis, followed by DNA cloning and sequencing.
In organisms ranging from yeast to mice, mutations in glucose or IGF-I-like signaling pathways extend life-span but also cause glycogen or fat accumulation and dwarfism.
Using rodent models of caloric restriction and genetic mouse models, e.g. the Ames and Snell dwarf mice, fat-specific insulin receptor knockout mice (FIRKO) and mice that are heterozygous for the IGF-I receptor (Igf1r+/-), investigators have shown that a reduction in plasma levels of insulin and/or IGF-I or reductions in insulin/IGF-I signalling appear to be correlated with increased longevity and retarded ageing.
We conclude that low IGF-1 is common in patients with JS and short stature, and that growth hormone status and possibly hypothalamic-pituitary function should be evaluated in this patient population.