Severe deficiencies of IGF-I, IGF-II, IGFBP-3, ALS and paradoxically high-normal bone mass in a child with insulin-resistance syndrome (Rabson-Mendenhall type)

Abstract Rabson-Mendenhall syndrome is a rare genetic disorder characterized by severe insulin resistance and hyperinsulinemia due to defects in signaling through the insulin receptor. Herein, we describe a new case of Rabson-Mendenhall syndrome in which investigations of the growth hormone (GH) – i...

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Bibliographic Details
Published in:Growth hormone & IGF research 2007-10, Vol.17 (5), p.399-407
Main Authors: Fowlkes, J.L, Bunn, R.C, Coleman, H.N, Hall, B, Reid, M.C, Thrailkill, K.M
Format: Article
Language:English
Subjects:
Advanced Basic Science
Body Height
Body Size
Body Weight
Bone Density
Child
Child, Preschool
Diabetes
DNA - genetics
DNA - isolation & purification
Donahue’s Syndrome
DXA
Endocrinology & Metabolism
Female
Growth
Growth hormone
Humans
Hyperinsulinism
Hyperinsulinism - genetics
Infant
Insulin receptor
Insulin Resistance - genetics
Insulin Resistance - physiology
Insulin-Like Growth Factor Binding Protein 3 - deficiency
Insulin-Like Growth Factor I - deficiency
Insulin-Like Growth Factor II - deficiency
Male
Pedigree
Protein Subunits
Syndrome
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Summary:Abstract Rabson-Mendenhall syndrome is a rare genetic disorder characterized by severe insulin resistance and hyperinsulinemia due to defects in signaling through the insulin receptor. Herein, we describe a new case of Rabson-Mendenhall syndrome in which investigations of the growth hormone (GH) – insulin-like growth factor (IGF) axis – reveal severe deficiencies in total and free insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding protein-3 (IGFBP-3), and the acid labile subunit (ALS). Based on these findings, we anticipated significant bone deficits, as have been described in other clinical scenarios in which the IGF axis is significantly perturbed. Long-bone studies revealed no gross malformations. Paradoxically, DXA scanning revealed a total body bone density Z -score of +2.0 (0.8 gm/cm2 ), suggesting an overall high-normal BMD for age and a high BMD corrected for bone or height age. The mechanisms by which BMD is protected from severe deficiencies in the IGF-axis are unknown, yet may involve enhanced IGF sensitivity, increased local production of IGFs, and/or supra-physiological concentrations of insulin substituting for the actions of IGFs in bone.
ISSN:1096-6374
1532-2238
DOI:10.1016/j.ghir.2007.04.007