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1.
The Clinical Spectrum of Resistance to Thyroid Hormone Alpha in Children and Adults.
Erbaş, İM, Demir, K
Journal of clinical research in pediatric endocrinology. 2021;(1):1-14
Abstract
Resistance to thyroid hormone alpha occurs due to pathogenic, heterozygous variants in THRA. The entity was first described in 2012 and to date only a small number of patients with varying severity have been reported. In this review, we summarize and interpret the heterogeneous clinical and laboratory features of all published cases, including ours. Many symptoms and findings are similar to those seen in primary hypothyroidism. However, thyroid-stimulating hormone levels are normal. Free triiodothyronine (T3) levels are in the upper half of normal range or frankly high and free thyroxine (T4) levels are low or in the lower half of normal range. Alterations in free T3 and free T4 may not be remarkable, particularly in adults, possibly contributing to underdiagnosis. In such patients, low reverse T3 levels, normo- or macrocytic anemia or, particularly in children, mildly elevated creatine kinase levels would warrant THRA sequencing. Treatment with L-thyroxine results in improvement of some clinical findings.
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2.
IGF-I deficiency and enhanced insulin sensitivity due to a mutated growth hormone receptor gene in humans.
Guevara-Aguirre, J, Torres, C, Peña, G, Palacios, M, Bautista, C, Guevara, A, Gavilanes, AW
Molecular and cellular endocrinology. 2021;:111044
Abstract
Human size is achieved by the coordinated expression of many genes. From conception to adulthood, a given genomic endowment is modified by highly variable environmental circumstances. During each stage of a person's life, distinct nutritional and hormonal influences continuously shape growing physical features until mature characteristics are attained. Underlying processes depend on precise provision of substrates and energy extracted by insulin action from nutrients, which allows cell proliferation, differentiation, and survival, under the concerted actions of growth hormone and insulin-like growth factor-I (IGF-I). It should be noted that growth and metabolic signaling pathways are interdependent and superimposed at multiple levels. Attainment of a fully developed human phenotype should be considered as a harmonious increment in body size rather than a simple increase in height. From this perspective we herein analyze adult features of individuals with an inactive growth hormone receptor, who consequently have severely diminished concentrations of serum insulin and endocrine IGF-I.
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3.
Auxological and endocrinological features in internationally adopted children.
Stagi, S, Papacciuoli, V, Boiro, D, Maggioli, C, Ndambao, NN, Losi, S, Chiappini, E, Toni, S, Ndiaye, O
Italian journal of pediatrics. 2020;(1):82
Abstract
In internationally adopted children disorders of linear growth, puberty development, thyroid function, and bone metabolism are frequently reported. It is important that these children receive careful auxological and endocrinological evaluations and follow-up.Pediatricians and other healthcare providers should be aware that auxological and endocrinological problems are common in newly arrived international adoptees.
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4.
Oesophageal atresia: The growth gap.
Traini, I, Menzies, J, Hughes, J, Leach, ST, Krishnan, U
World journal of gastroenterology. 2020;(12):1262-1272
Abstract
Poor growth is an under-recognised yet significant long-term sequelae of oesophageal atresia (OA) repair. Few studies have specifically explored the reasons for growth impairment in this complex cohort. The association between poor growth with younger age and fundoplication appears to have the strongest supportive evidence, highlighting the need for early involvement of a dietitian and speech pathologist, and consideration of optimal medical reflux management prior to referring for anti-reflux surgery. However, it remains difficult to reach conclusions regarding other factors which may negatively influence growth, due to conflicting findings, inconsistent definitions and lack of validated tool utilisation. While swallowing and feeding difficulties are particularly frequent in younger children, their relationship with growth remains unclear. It is possible that these morbidities impact on the diet of children with OA, but detailed analysis of dietary composition and quality, and its relationship with these complications and growth, has not yet been conducted. Another potential area of research in OA is the role of the microbiota in growth and nutrition. While the microbiota has been linked to growth impairment in other paediatric conditions, it is yet to be investigated in OA. Further research is needed to identify the most important contributory factors to poor growth, the role of the intestinal microbiota, and effective interventions to maximise growth and nutritional outcomes in this cohort.
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5.
Δ1 -Pyrroline-5-carboxylate synthetase deficiency: An emergent multifaceted urea cycle-related disorder.
Marco-Marín, C, Escamilla-Honrubia, JM, Llácer, JL, Seri, M, Panza, E, Rubio, V
Journal of inherited metabolic disease. 2020;(4):657-670
Abstract
The bifunctional homooligomeric enzyme Δ1 -pyrroline-5-carboxylate synthetase (P5CS) and its encoding gene ALDH18A1 were associated with disease in 1998. Two siblings who presented paradoxical hyperammonemia (alleviated by protein), mental disability, short stature, cataracts, cutis laxa, and joint laxity, were found to carry biallelic ALDH18A1 mutations. They showed biochemical indications of decreased ornithine/proline synthesis, agreeing with the role of P5CS in the biosynthesis of these amino acids. Of 32 patients reported with this neurocutaneous syndrome, 21 familial ones hosted homozygous or compound heterozygous ALDH18A1 mutations, while 11 sporadic ones carried de novo heterozygous ALDH18A1 mutations. In 2015 to 2016, an upper motor neuron syndrome (spastic paraparesis/paraplegia SPG9) complicated with some traits of the neurocutaneous syndrome, although without report of cutis laxa, joint laxity, or herniae, was associated with monoallelic or biallelic ALDH18A1 mutations with, respectively, dominant and recessive inheritance. Of 50 SPG9 patients reported, 14 and 36 (34/2 familial/sporadic) carried, respectively, biallelic and monoallelic mutations. Thus, two neurocutaneous syndromes (recessive and dominant cutis laxa 3, abbreviated ARCL3A and ADCL3, respectively) and two SPG9 syndromes (recessive SPG9B and dominant SPG9A) are caused by essentially different spectra of ALDH18A1 mutations. On the bases of the clinical data (including our own prior patients' reports), the ALDH18A1 mutations spectra, and our knowledge on the P5CS protein, we conclude that the four syndromes share the same pathogenic mechanisms based on decreased P5CS function. Thus, these syndromes represent a continuum of increasing severity (SPG9A < SPG9B < ADCL3 ≤ ARCL3A) of the same disease, P5CS deficiency, in which the dominant mutations cause loss-of-function by dominant-negative mechanisms.
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6.
Repercussions of inborn errors of immunity on growth.
Goudouris, ES, Segundo, GRS, Poli, C
Jornal de pediatria. 2019;:49-58
Abstract
OBJECTIVES This study aimed to review the literature on the repercussions of the different inborn errors of immunity on growth, drawing attention to the diagnosis of this group of diseases in patients with growth disorders, as well as to enable the identification of the different causes of growth disorders in patients with inborn errors of immunity, which can help in their treatment. DATA SOURCES Non-systematic review of the literature, searching articles since 2000 in PubMed with the terms "growth", "growth disorders", "failure to thrive", or "short stature" AND "immunologic deficiency syndromes", "immune deficiency disease", or "immune deficiency" NOT HIV. The Online Mendelian Inheritance in Man (OMIN) database was searched for immunodeficiencies and short stature or failure to thrive. DATA SUMMARY Inborn errors of immunity can affect growth in different ways, and some of them can change growth through multiple simultaneous mechanisms: genetic syndromes; disorders of the osteoarticular system; disorders of the endocrine system; reduction in caloric intake; catabolic processes; loss of nutrients; and inflammatory and/or infectious conditions. CONCLUSIONS The type of inborn errors of immunity allows anticipating what type of growth disorder can be expected. The type of growth disorder can help in the diagnosis of clinical conditions related to inborn errors of immunity. In many inborn errors of immunity, the causes of poor growth are mixed, involving more than one factor. In many cases, impaired growth can be adjusted with proper inborn errors of immunity treatment or proper approach to the mechanism of growth impairment.
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7.
Environmental enteric dysfunction and child stunting.
Budge, S, Parker, AH, Hutchings, PT, Garbutt, C
Nutrition reviews. 2019;(4):240-253
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Abstract
In 2017, an estimated 1 in every 4 (23%) children aged < 5 years were stunted worldwide. With slow progress in stunting reduction in many regions and the realization that a large proportion of stunting is not due to insufficient diet or diarrhea alone, it remains that other factors must explain continued growth faltering. Environmental enteric dysfunction (EED), a subclinical state of intestinal inflammation, can occur in infants across the developing world and is proposed as an immediate causal factor connecting poor sanitation and stunting. A result of chronic pathogen exposure, EED presents multiple causal pathways, and as such the scope and sensitivity of traditional water, sanitation, and hygiene (WASH) interventions have possibly been unsubstantial. Although the definite pathogenesis of EED and the mechanism by which stunting occurs are yet to be defined, this paper reviews the existing literature surrounding the proposed pathology and transmission of EED in infants and considerations for nutrition and WASH interventions to improve linear growth worldwide.
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8.
Biomarkers of GH action in children and adults.
Schilbach, K, Olsson, DS, Boguszewski, MCS, Bidlingmaier, M, Johannsson, G, Jørgensen, JL
Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 2018;:1-8
Abstract
Growth hormone (GH) and IGF-I levels in serum are used as biomarkers in the diagnosis and management of GH-related disorders but have not been subject to structured validation. Auxological parameters in children and changes in body composition in adults, as well as metabolic parameters and patient related outcomes are used as clinical and surrogate endpoints. New treatment options, such as long acting GH and GH antagonists, require reevaluation of the currently used biochemical biomarkers. This article will review biomarkers, surrogate endpoints and clinical endpoints related to GH treatment in children and adults as well as in acromegaly.
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9.
Genetic causes of proportionate short stature.
Argente, J, Pérez-Jurado, LA
Best practice & research. Clinical endocrinology & metabolism. 2018;(4):499-522
Abstract
Human growth is a very complex phenomenon influenced by genetic, hormonal, nutritional and environmental factors, from fetal life to puberty. Although the GH-IGF axis has a central role with specific actions on growth, numerous genes are involved in the control of stature. Genome-wide association studies have identified >600 variants associated with human height, still explaining only a small fraction of phenotypic variation. Since short stature in childhood is a common reason for referral, pediatric endocrinologists must be aware of the multifactorial and polygenic contributions to height. Multiple disorders characterized by growth failure of prenatal and/or postnatal onset due to single gene defects have been described. Their early diagnosis, facilitated by advances in genomic technologies, is of upmost importance for their clinical management and to provide genetic counseling. Here we review the current clinical and genetic information regarding different syndromes and hormone abnormalities with proportionate short stature as the main feature, and provide an update of the approach for diagnosis and management.
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10.
Nutritional status and dietary intakes of children amid the nutrition transition: the case of the Eastern Mediterranean Region.
Nasreddine, LM, Kassis, AN, Ayoub, JJ, Naja, FA, Hwalla, NC
Nutrition research (New York, N.Y.). 2018;:12-27
Abstract
The Eastern Mediterranean Region (EMR) is undergoing social and economic changes that may impact the nutritional status of children living in its countries. The objective of this review is to evaluate the nutritional status and dietary intakes of children (0-12 years) in selected EMR countries, namely, Jordan, Lebanon, Kingdom of Saudi Arabia (KSA), and the United Arab Emirates. MedLine, PubMed, Scopus, and Google Scholar were searched for relevant articles published between 1990 and 2016; international organizations and governmental websites were also searched. Stunting in the region was estimated at 7.3% to 9.3%, wasting at 1.1% to 11.8%, and underweight at 1.6% to 5.3%. In contrast, overweight and obesity affected 19% to 21% of school-aged children from Lebanon and KSA. Available biochemical data showed that pediatric anemia, vitamin A, and vitamin D deficiencies remain a challenge in the region. Dietary intake studies have identified inadequate intakes of iron, calcium, zinc, folic acid, vitamin A, and vitamin D, concurrently with high intakes of fat, saturated fat, and sugar. This review provides valuable insight into the nutrition situation of children in 2 major areas of the EMR, the Levant and the Gulf, and identified several gaps and challenges in existing nutritional assessment studies. Key issues include the triple burden of malnutrition in this age group (underweight, nutrient inadequacies, and overweight/obesity), while calling for integrated action to improve the nutritional status of children in countries of the region. Opportunities for future research include nationwide nutritional and dietary surveys in countries where the largest data gaps remain such as the United Arab Emirates and KSA.