Growth failure in a child showing characteristics of Seckel syndrome: possible effects of IGF-I and endogenous IGFBP-3.
Seckel syndrome is an autosomal-recessive disorder with a frequency of less than 1/10 000 births in which there are multiple malformations including severe short stature. We report on a patient with Seckel syndrome with a current body height of -7.5 SDS. Laboratory investigations at the age of 19 months revealed high levels of IGF-I, IGF-II and IGFBP-3. These data suggested the existence of IGF-I resistance possibly caused by impairment of the IGF-I receptor (IGF-IR) or altered IGFBPs. The purpose of this investigation was to examine whether the growth retardation in a Seckel syndrome patient is related to an alteration in the IGF system. Analysis of IGF-IR mRNA of patient's and control fibroblasts by solution hybridization/RNase protection assay did not show differences of IGF-IR transcript expression or size. Affinity crosslinking studies using [125I]-IGF-I showed normal-sized IGF-IR-ligand complexes. Mutation analysis of the complete coding regions of the IGF-I and IGF-IR genes showed no evidence of genetic alterations. Ligand blot analysis of IGFBPs secreted by the patient's fibroblasts showed stronger signals than control cells. Quantitative measurement of IGFBP-3 in cell-conditioned media was performed by radioimmunoassay (RIA) and revealed a sixfold increase when compared to control fibroblasts. We conclude that in this patient with Seckel syndrome and severe growth impairment IGF-I resistance is possibly related to altered production of IGFBP-3.
Schmidt
A
A
Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany. schmia@medizin.uni-leipzig.de
Chakravarty
A
A
Brommer
E
E
Fenne
B D
BD
Siebler
T
T
De Meyts
P
P
Kiess
W
W
D000015:Abnormalities, Multiple / Q000378:metabolism*; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006130:Growth Disorders / Q000378:metabolism*; D006801:Humans; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D013577:Syndrome
D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II