Head circumference in untreated and IGF-I treated patients with Laron syndrome

Laron, Zvi; Iluz, M.; Kauli, Rivka

doi:10.1016/j.ghir.2012.02.005

Cited by 19 publications

(4 citation statements)

References 20 publications

(22 reference statements)

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“…It is noteworthy that the mean head circumference SDS before treatment was less retarded than that described by Laron et al [27] (-2.5 vs. -3.3, respectively), and the increase noted with therapy (though significant) was also less than that reported by their group but comparable to the values published by Backeljauw and Underwood [3,19]. …”

Section: Discussionsupporting

confidence: 71%

Further Observations on the Effects of Long-Term Treatment with Recombinant Human Insulin-Like Growth Factor 1 in Growth Hormone Insensitivity Syndrome

Kholy¹,

Amr²,

Elsedfy³

2014

Horm Res Paediatr

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Background/Aim: Growth hormone insensitivity syndrome (GHIS) is a spectrum of disorders. Laron syndrome was the earliest discovered. Insulin-like growth factor 1 (IGF-1) therapy is used to improve growth. IGF-1 has diverse effects on the growth of body organs. We aim to assess the long-term effects of IGF-1 therapy in patients with GHIS particularly on adiposity and acral growth. Methods: Six patients (5 with Laron syndrome and 1 with type 1A growth hormone deficiency) were followed for a mean (±SD) of 8.2 ± 1.8 years. Mean age at start of therapy was 7.6 ± 4.1 years. Anthropometric evaluation including growth of hand, foot, ear, and skin folds, and assessment of internal organ growth were done. Results: Hand and foot sizes improved significantly, especially when treatment was initiated early. Prominent effects on adiposity were observed, reflected by increment in body mass index standard deviation score (SDS) and skin fold SDS. Mean height, height velocity, sitting height, and head circumference SDS improved with therapy. A significant increase in spleen and right kidney was appreciated. Conclusion: IGF-1 therapy improves growth in GHIS. The hand and foot sizes increase significantly with therapy, and can even normalize with early initiation of treatment. Ear length further improves with therapy. Other effects include increase in adiposity and internal organ growth.

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Section: Discussionsupporting

confidence: 71%

Further Observations on the Effects of Long-Term Treatment with Recombinant Human Insulin-Like Growth Factor 1 in Growth Hormone Insensitivity Syndrome

Kholy¹,

Amr²,

Elsedfy³

2014

Horm Res Paediatr

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“…Whether the reduced head circumference was a consequence of the AD STAT5B mutation or, more likely, caused by additional genetic variants, remains unclear, but no obvious recessive or dominant candidate variants were revealed from available exome data. It is notable that the relatively normal head circumferences, albeit below the mean, of patients from families 1 and 2 were comparable to those observed in patients with GHIS 42 (Supplementary Fig. 3 ).…”

Section: Discussionsupporting

confidence: 60%

Dominant-negative STAT5B mutations cause growth hormone insensitivity with short stature and mild immune dysregulation

et al. 2018

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Growth hormone (GH) insensitivity syndrome (GHIS) is a rare clinical condition in which production of insulin-like growth factor 1 is blunted and, consequently, postnatal growth impaired. Autosomal-recessive mutations in signal transducer and activator of transcription (STAT5B), the key signal transducer for GH, cause severe GHIS with additional characteristics of immune and, often fatal, pulmonary complications. Here we report dominant-negative, inactivating STAT5B germline mutations in patients with growth failure, eczema, and elevated IgE but without severe immune and pulmonary problems. These STAT5B missense mutants are robustly tyrosine phosphorylated upon stimulation, but are unable to nuclear localize, or fail to bind canonical STAT5B DNA response elements. Importantly, each variant retains the ability to dimerize with wild-type STAT5B, disrupting the normal transcriptional functions of wild-type STAT5B. We conclude that these STAT5B variants exert dominant-negative effects through distinct pathomechanisms, manifesting in milder clinical GHIS with general sparing of the immune system.

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“…From a mechanistic point of view and in accordance with the early protein hypothesis, the protein-induced growth of the brain and heart is likely mediated by IGF-1 (as is the case in the kidney) because IGF-1 has been shown to mediate cardiac hypertrophy in acromegaly 60 and brain growth in Laron syndrome. 61 …”

Section: Can Protein Intake In Infancy Affect Other Tissues?mentioning

confidence: 99%

Early Programming by Protein Intake: The Effect of Protein on Adiposity Development and the Growth and Functionality of Vital Organs

Luque

Closa‐Monasterolo

Escribano

et al. 2015

Nutr Metab Insights

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This article reviews the role of protein intake on metabolic programming early in life. The observations that breastfeeding in infancy reduces the risk of being overweight and obese later in life and the differences in the protein content between formula milk and human milk have generated the early protein hypothesis. The present review focuses on a mechanistic approach to programmed adiposity and the growth and development of other organs by protein intake in infancy, which may be mediated by branched-chain amino acids, insulin, and insulin-like growth factor 1 via the mammalian target of rapamycin. Observational studies and clinical trials have shown that lowering the protein content in infant and follow-on formulas may reduce the risk of becoming obese later in life. The recent body of evidence is currently being translated into new policies. Therefore, the evolution of European regulatory laws and recommendations by expert panels on the protein content of infant and follow-on formulas are also reviewed. Research gaps, such as the critical window for programming adiposity by protein intake, testing formulas with modified amino acids, and the long-term consequences of differences in protein intake on organ functionality among well-nourished infants, have been identified.

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Head circumference in untreated and IGF-I treated patients with Laron syndrome

Cited by 19 publications

References 20 publications

Further Observations on the Effects of Long-Term Treatment with Recombinant Human Insulin-Like Growth Factor 1 in Growth Hormone Insensitivity Syndrome

Further Observations on the Effects of Long-Term Treatment with Recombinant Human Insulin-Like Growth Factor 1 in Growth Hormone Insensitivity Syndrome

Dominant-negative STAT5B mutations cause growth hormone insensitivity with short stature and mild immune dysregulation

Early Programming by Protein Intake: The Effect of Protein on Adiposity Development and the Growth and Functionality of Vital Organs

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