Laron's dwarfism: Studies on the nature of the defect

Elders, M. Joycelyn; Garland, John T.; Daughaday, William; Fisher, Delbert A.; Whitney, John M.; Hughes, Edwin R.

doi:10.1016/s0022-3476(73)80485-8

Cited by 48 publications

(12 citation statements)

References 19 publications

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“…Subsequent studies revealed that these patients cannot generate IGF-1. 35 This syndrome of GH resistance (insensitivity) was named by Elders et al as Laron dwarfism, 36 a name subsequently changed to Laron syndrome (LS). 37 Molecular studies revealed that the causes of GH resistance are deletions 38 or mutations 39 in the GH receptor gene, resulting in the failure to generate IGF-1 and a reduction in the synthesis of several other substances, including IGFBP-3.…”

Section: Igf Binding Proteins (Igfbps)mentioning

confidence: 99%

Insulin-like growth factor 1 (IGF-1): a growth hormone

Laron

2001

Molecular Pathology

488

303

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Aim-To contribute to the debate about whether growth hormone (GH) and insulin-like growth factor 1 (IGF-1) act independently on the growth process. Methods-To describe growth in human and animal models of isolated IGF-1 deficiency (IGHD), such as in Laron syndrome (LS; primary IGF-1 deficiency and GH resistance) and IGF-1 gene or GH receptor gene knockout (KO) mice. Results-Since the description of LS in 1966, 51 patients were followed, many since infancy. Newborns with LS are shorter (42-47 cm) than healthy babies (49-52 cm), suggesting that IGF-1 has some influence on intrauterine growth. Newborn mice with IGF-1 gene KO are 30% smaller. The postnatal growth rate of patients with LS is very slow, the distance from the lowest normal centile increasing progressively. If untreated, the final height is 100-136 cm for female and 109-138 cm for male patients. They have acromicia, organomicria including the brain, heart, gonads, genitalia, and retardation of skeletal maturation. The availability of biosynthetic IGF-1 since 1988 has enabled it to be administered to children with LS. It accelerated linear growth rates to 8-9 cm in the first year of treatment, compared with 10-12 cm/year during GH treatment of IGHD. The growth rate in following years was 5-6.5 cm/year. Conclusion-IGF-1 is an important growth hormone, mediating the protein anabolic and linear growth promoting eVect of pituitary GH. It has a GH independent growth stimulating eVect, which with respect to cartilage cells is possibly optimised by the synergistic action with GH. (J Clin Pathol: Mol Pathol 2001;54:311-316)

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Section: Igf Binding Proteins (Igfbps)mentioning

confidence: 99%

Insulin-like growth factor 1 (IGF-1): a growth hormone

Laron

2001

Molecular Pathology

488

303

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“…In 1966, investigators from our Institute described a new syndrome of familial dwarf ism [16] which subsequently came to be termed Laron-type dwarfism [LTD] in the literature [6], In its clinical picture and in many of the laboratory findings, it is indistin guishable from isolated growth hormone de ficiency (1GHD) [18], but it is characterized by high levels of plasma immunoreactive hu man growth hormone (IR-hGH) and low lev els of serum somatomedin [19], Since then additional patients have been reported from our Institute [20] and by others [4,15,24,26,29], This syndrome was first suspected to be caused by an abnormal hGH molecule [16], but later evidence pointed towards resistance to exogenous hGH [5,6,10,19,21] and to an abnormality in the hGH receptors [8]. In the present investigation we compared binding conditions of plasma hGH of normal, acro megalic and LTD patients to hGH receptors in human liver microsomes.…”

Section: Introductionmentioning

confidence: 99%

Some Properties of the Plasma hGH Activity in Patients with Laron-Type Dwarfism Determined by a Radioreceptor Assay Using Human Liver Tissue

et al. 1985

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A radioreceptor assay for human growth hormone (hGH) using the 100,000-g pellet of human liver tissue homogenates obtained from a 13-year-old male donor of a kidney transplantation is described. The dilution curves of the plasma hGH of 6 patients with Laron-type dwarfism (LTD) as well as those of the plasma hGH from 1 normal child and 2 acromegalic patients were all found to be parallel to the standard curve, suggesting that in the LTD syndrome the circulating hGH is biologically active.

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“…Laron was aware of 43 other patients in non-Jewish populations (3), and some 30 of these have been reported. They include patients from Lebanon (4), Pakistan (5), Spain (6), Tunisia (7), Italy (8,9), Mexico (10), France (9), Denmark (I 1), the Netherlands (12), Saudi Arabia (13), Sardinia (14), Canada (15), Brazil (16), and the USA (17,18). A group of 20 patients with a distorted sex distribution (19 female: I male) from Loja province in southern Ecuador was reported recently (19).…”

mentioning

confidence: 99%

“…As a result of these observations, we prefer to designate this form of GH insensitivity as GH receptor deficiency (GHRD), in view of the location-of the defect. If eponymic designation is used, this condition should be referred to as Laron syndrome (11), rather than Laron-type ·dwarfism (13). Categorical terms, such as 'midget' and 'dwarf, that tend to brand the person on the basis of size and proportion alone should be abandoned (28).…”

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confidence: 99%