Laron-type dwarfism with apparently normal high affinity serum growth hormone-binding protein.
OBJECTIVE
Normal serum contains a high affinity GH-binding protein, which appears to be identical with the extracellular domain of the GH receptor. It is normally absent from the serum of patients with Laron-type dwarfism. We wished in this study to define the serum GH-binding protein status of a family with Laron-type dwarfism.


METHODS
We performed an open case study of an Asian family in which three sisters (aged 3 to 15 years) had the phenotype of Laron-type dwarfism. Sera from a fourth, unrelated girl with Laron-type dwarfism and subjects without endocrine disorders were used as control samples.


METHODS
Laron-type dwarfism was confirmed by demonstration of elevated serum GH levels and low serum IGF-I levels on immunoassay, with serum IGF-I levels failing to rise during treatment with GH. Serum GH-binding proteins were characterized using gel chromatography on Sephacryl S-100HR following incubation of serum with 125I-GH, Scatchard analysis of ligand binding, and by polyacrylamide gel electrophoresis after covalent cross-linking to 125I-GH.


RESULTS
All members of the family had high affinity serum GH-binding protein activity similar in size, circulating levels and apparent affinity for GH to that of normal subjects. This contrasted with the very low serum GH-binding protein activity in the unrelated child with Laron-type dwarfism and previous reports of serum GH-binding protein levels in this disorder.


CONCLUSIONS
The affected patients may possess a novel biochemical defect which results in GH-resistance and reduced production of IGF-I in the presence of normal serum GH-binding protein levels.
Buchanan
C R
CR
Department of Growth and Development, Institute of Child Health, London, UK.
Maheshwari
H G
HG
Norman
M R
MR
Morrell
D J
DJ
Preece
M A
MA
D000293:Adolescent; D002648:Child; D002850:Chromatography, Gel; D004392:Dwarfism / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000032:analysis* / Q000378:metabolism
D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone