title: 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) - 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/cm(2)), 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.
authors.affiliation: Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, 800 Marshall Street, Slot 512-6, Little Rock, AR 72202, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Fowlkes
authors.forename: R C
authors.initials: RC
authors.lastname: Bunn
authors.forename: H N
authors.initials: HN
authors.lastname: Coleman
authors.forename: B
authors.initials: B
authors.lastname: Hall
authors.forename: M C
authors.initials: MC
authors.lastname: Reid
authors.forename: K M
authors.initials: KM
authors.lastname: Thrailkill
mesh_terms: D001827:Body Height; D049628:Body Size; D001835:Body Weight; D015519:Bone Density; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000235:genetics*; D007223:Infant; D007333:Insulin Resistance / Q000235:genetics* / Q000502:physiology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000172:deficiency*; D007334:Insulin-Like Growth Factor I / Q000172:deficiency*; D007335:Insulin-Like Growth Factor II / Q000172:deficiency*; D008297:Male; D010375:Pedigree; D021122:Protein Subunits; D013577:Syndrome
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D021122:Protein Subunits; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D004247:DNA