The Laron syndrome , also known as primary GH insensitivity , GH receptor deficiency , short stature due to growth hormone resistance , primary growth hormone insensitivity or growth hormone receptor deficiency called, is a rare, autosomal - recessive inherited disease that primarily by manifested a short stature in the affected patients.
Laron's syndrome is an extremely rare hereditary disease. Around 200 to 300 cases have been described worldwide so far.
Clinical picture and diagnostics
Patients with Laron's syndrome have a congenital lack of functional receptors for the growth hormone somatotropin. Due to a genetic defect in the somatotropin receptor (GHR, growth hormone receptor ), the somatotropin (GH, growth hormone ) cannot activate the expression of the insulin-like growth factor 1 (IGF-I, insulin-like growth factor I ).
Short stature, facial deformities , trunk-dominated obesity , late onset of puberty and recurrent hypoglycaemia are typical for Laron syndrome. In plasma extremely low levels found for the IGF-1 and significantly elevated levels of somatotropin. Somatotropin-binding protein (GHBP), the soluble isoform of GHR, is either severely depleted in plasma or completely absent or inoperable.
Children are more susceptible to infection.
The greatly reduced release of IGF-I not only causes short stature. Patients with Laron syndrome have a significantly reduced chance of developing cancer , acne and diabetes mellitus . Even the aging takes place slowly. An Ecuadorian population in the province of Loja of 99 patients with Laron syndrome was medically monitored for 22 years. One non-lethal malignancy and no case of diabetes mellitus were observed in this group during this period . In the control group, however, the prevalence for cancer was 17% and for diabetes 5%. These epidemiological data lead to speculation as to whether artificially lowering IGF-1 levels could slow aging and reduce the likelihood of developing cancer.
The GHR - gene , which for the growth hormone receptor encoded , is located in humans on chromosome 5 , locus p13-p12. The gene product consists of 638 amino acids and is membrane-bound . The mutations in the GHR can either prevent the binding of GH to the extracellular domain (ectodomain) or block the dimerization of the receptor after the somatotropin has docked. Both of these factors mean that the cells of the affected patients express only very small amounts of IGF-1.
The defects in the GHR gene that can lead to Laron syndrome are heterogeneous and include gene deletions , as well as nonsense, missense, frameshift and splice-site mutations, as well as repeating CpG dinucleotide substitutions, all of which are essentially the affect extracellular domains of GHR. A total of over 30 different GHR-deactivating mutations were found.
Treatment and prognosis
Since 1986, biotechnologically produced IGF-I (rhIGF-I, recombinant human IGF-I) has been available in sufficient quantities so that children affected by Laron syndrome can be treated with it. The prognosis is favorable - even without treatment. Apart from the daily handicaps caused by short stature, patients can lead a largely normal life.
Laron's syndrome was first described in 1966 by a working group led by the Israeli child endocrinologist Zvi Laron (* 1927). The disease was named after him. The clinical investigations began as early as 1958 on a group of small children who had high levels of growth hormones in the serum. Then the cause of the disease was identified as a molecular defect in the growth hormone receptor (somatotropin receptor).
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Popular science articles
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- Laron's syndrome: short stature protects against cancer and diabetes. In: Ärzteblatt of February 18, 2011
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- UniProt P10912
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