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Cardiovascular disease is one of the most important complications in girls and women with Turner syndrome (TS). Although the latest international guideline provides useful suggestions for the management of cardiovascular diseases in TS, some unknown cardiac conditions warrant physicians' attention and awareness. Here, we have reported two adult cases wherein significant cardiovascular diseases were detected during the transition period. The first case patient was diagnosed with aortic crank deformity and left subclavian artery aneurysm at 14 years based on the report of cardiac catheterization, computed tomography angiography, and cardiac magnetic resonance imaging, which had remained undetected by annual evaluations using transthoracic echocardiography (TTE). This case emphasizes the importance of cardiac reevaluation during the transition period. The second case patient was diagnosed with moderate mitral valve regurgitation (MR) due to mitral valve prolapse at 18 years through TTE, although the first evaluation at 7 years by TTE detected slight MR without any clinical concerns. The condition however progressed to severe MR at 28 years, requiring mitral valvuloplasty. MR is the most common valve disease worldwide, which makes it challenging to comprehend whether the condition is a complication. However, the condition requiring surgery at this age is extremely rare, which implies the possibility of early progression. Because almost all literature on cardiovascular complications in TS is cross-sectional, further information about longitudinal cardiovascular conditions is vital for optimal care for girls and women with TS. The two cases reported in this article provide significant information for improving lifelong cardiovascular health issues in TS.
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Síndrome de Turner , Humanos , Síndrome de Turner/complicaciones , Síndrome de Turner/terapia , Femenino , Adulto , Adolescente , Ecocardiografía , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/terapia , Enfermedades Cardiovasculares/etiologíaRESUMEN
CONTEXT: Thyroglobulin (Tg), encoded by TG, is essential for thyroid hormone synthesis. TG defects result in congenital hypothyroidism (CH). Most reported patients were born before the introduction of newborn screening (NBS). OBJECTIVE: We aimed to clarify the phenotypic features of patients with TG defects diagnosed and treated since the neonatal period. METHODS: We screened 1061 patients with CH for 13 CH-related genes and identified 30 patients with TG defects. One patient was diagnosed due to hypothyroidism-related symptoms and the rest were diagnosed via NBS. Patients were divided into 2 groups according to their genotypes, and clinical characteristics were compared. We evaluated the functionality of the 7 missense variants using HEK293 cells. RESULTS: Twenty-seven rare TG variants were detected, including 15 nonsense, 3 frameshift, 2 splice-site, and 7 missense variants. Patients were divided into 2 groups: 13 patients with biallelic truncating variants and 17 patients with monoallelic/biallelic missense variants. Patients with missense variants were more likely to develop thyroid enlargement with thyrotropin stimulation than patients with biallelic truncating variants. Patients with biallelic truncating variants invariably required full hormone replacement, whereas patients with missense variants required variable doses of levothyroxine. Loss of function of the 7 missense variants was confirmed in vitro. CONCLUSION: To our knowledge, this is the largest investigation on the clinical presentation of TG defects diagnosed in the neonatal period. Patients with missense variants showed relatively mild hypothyroidism with compensative goiter. Patients with only truncating variants showed minimal or no compensative goiter and required full hormone replacement.
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Hipotiroidismo Congénito , Estudios de Asociación Genética , Tamizaje Neonatal , Tiroglobulina , Humanos , Hipotiroidismo Congénito/genética , Hipotiroidismo Congénito/diagnóstico , Femenino , Masculino , Tiroglobulina/genética , Recién Nacido , Japón/epidemiología , Preescolar , Mutación Missense , Lactante , Niño , Fenotipo , Genotipo , Células HEK293 , Pueblos del Este de AsiaRESUMEN
Measurements of serum insulin-like growth factor 1 (IGF-1) levels are useful surrogate markers for the diagnosis and management of patients with growth hormone-related disorders. We have previously published normative data of serum IGF-1 levels for the Japanese population aged 0-77 years by combining and analyzing previously reported references, which were separately and independently constructed, to properly reflect data in the transition period. Although the reference is widely used in both clinical and research settings, the reference did not include data for those aged >77 years, raising the question of how we would evaluate patients over those ages. In this study, we extended the age- and sex-specific reference ranges of serum IGF-1 levels to the age of 80 years by reanalyzing combined data on serum IGF-1 levels from previously published references. Based on our results, we proposed that individuals aged >80 years can be evaluated using the references set at the age of 80 years. However, our proposal was based on a very limited number of participants. Therefore, physicians should exercise caution when interpreting IGF-1 standard deviation scores for those aged >80 years because they are not exactly correct but acceptable.
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Factor I del Crecimiento Similar a la Insulina , Femenino , Humanos , Masculino , Pueblos del Este de Asia , Trastornos del Crecimiento , Hormona del Crecimiento/metabolismo , Hormona de Crecimiento Humana/metabolismo , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina , Factor I del Crecimiento Similar a la Insulina/análisis , Factor I del Crecimiento Similar a la Insulina/metabolismo , Valores de Referencia , Anciano de 80 o más AñosRESUMEN
[This corrects the article DOI: 10.1297/cpe.25.71.].
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[This corrects the article DOI: 10.1297/cpe.26.153.].
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Bone strength is determined by the structure and composition of its thickened outer shell (cortical bone), yet the mechanisms controlling cortical consolidation are poorly understood. Cortical bone maturation depends on SOCS3-mediated suppression of IL-6 cytokine-induced STAT3 phosphorylation in osteocytes, the cellular network embedded in bone matrix. Because SOCS3 also suppresses granulocyte-colony-stimulating factor receptor (G-CSFR) signaling, we here tested whether global G-CSFR (Csf3r) ablation altereed bone structure in male and female mice lacking SOCS3 in osteocytes, (Dmp1Cre :Socs3f/f mice). Dmp1Cre :Socs3f/f :Csf3r-/- mice were generated by crossing Dmp1Cre :Socs3f/f mice with Csf3r-/- mice. Although G-CSFR is not expressed in osteocytes, Csf3r deletion further delayed cortical consolidation in Dmp1Cre :Socs3f/f mice. Micro-CT images revealed extensive, highly porous low-density bone, with little true cortex in the diaphysis, even at 26 weeks of age; including more low-density bone and less high-density bone in Dmp1Cre :Socs3f/f :Csf3r-/- mice than controls. By histology, the area where cortical bone would normally be found contained immature compressed trabecular bone in Dmp1Cre :Socs3f/f :Csf3r-/- mice and greater than normal levels of intracortical osteoclasts, extensive new woven bone formation, and the presence of more intracortical blood vessels than the already high levels observed in Dmp1Cre :Socs3f/f controls. qRT-PCR of cortical bone from Dmp1Cre :Socs3f/f :Csf3r-/- mice also showed more than a doubling of mRNA levels for osteoclasts, osteoblasts, RANKL, and angiogenesis markers. The further delay in cortical bone maturation was associated with significantly more phospho-STAT1 and phospho-STAT3-positive osteocytes, and a threefold increase in STAT1 and STAT3 target gene mRNA levels, suggesting G-CSFR deletion further increases STAT signaling beyond that of Dmp1Cre :Socs3f/f bone. G-CSFR deficiency therefore promotes STAT1/3 signaling in osteocytes, and when SOCS3 negative feedback is absent, elevated local angiogenesis, bone resorption, and bone formation delays cortical bone consolidation. This points to a critical role of G-CSF in replacing condensed trabecular bone with lamellar bone during cortical bone formation. © 2022 American Society for Bone and Mineral Research (ASBMR).
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Factor Estimulante de Colonias de Granulocitos , Osteocitos , Receptores de Factor Estimulante de Colonias de Granulocito , Factor de Transcripción STAT3 , Animales , Femenino , Masculino , Ratones , Hueso Cortical/diagnóstico por imagen , Factor Estimulante de Colonias de Granulocitos/genética , Interleucina-6 , Osteocitos/patología , ARN Mensajero , Factor de Transcripción STAT3/metabolismoRESUMEN
Growth hormone (GH) deficiency (GHD) in children is a heterogeneous condition that includes several entities of various severities. GH treatment has been affected by various factors. Because comprehensive analyses for Japanese children with GHD over time are scarce, we investigated the baseline characteristics of patients with GHD at the start of GH treatment between 1996 and 2015 using data from the Foundation for Growth Science in Japan. During the registration period, 19,717 subjects were determined to be eligible for GH treatment as GHD. Overall analyses revealed that there were twice the number of male patients as female patients, and the etiology was idiopathic in 91.1%, central nervous system (CNS) tumor at the hypothalamus-pituitary area in 1.7%, CNS tumor distant from the hypothalamus-pituitary area in 0.68%, other tumors in 0.91%, congenital CNS malformations in 0.83%, and other diseases in 1.1% with their specific characteristics. The latest average age, height standard deviation score (SDS), insulin-like growth factor-1 SDS, and proportion of severe GHD at GH treatment initiation were 8.8 years, -2.76, -1.42, and 19.5%, respectively. The proportions of breech delivery and asphyxia gradually decreased, whereas that of caesarean section gradually increased during the registration period with the latest values of 2.2%, 4.9%, and 14.0%, respectively (all analyses: p < 0.0001). In contrast, the proportion of idiopathic GHD with breech delivery seemed to reach the lowest level among those with a birth year before 2000. This study identified the characteristics and changes of patients with GHD over 20 years.
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Enanismo Hipofisario , Hormona de Crecimiento Humana , Estatura , Cesárea , Niño , Demografía , Femenino , Hormona del Crecimiento , Humanos , Japón , Masculino , EmbarazoRESUMEN
Turner syndrome (TS) is a chromosomal disorder affecting females characterized by short stature and gonadal dysgenesis. Untreated girls with TS reportedly are approximately 20-cm shorter than normal girls within their respective populations. The growth patterns of girls with TS also differ from those of the general population. They are born a little smaller than the normal population possibly due to a mild developmental delay in the uterus. After birth, their growth velocity declines sharply until 2 years of age, then continues to decline gradually until the pubertal age of normal children and then drops drastically around the pubertal period of normal children because of the lack of a pubertal spurt. After puberty, their growth velocity increases a little because of the lack of epiphyseal closure. A secular trend in height growth has been observed in girls with TS so growth in excess of the secular trend should be used wherever available in evaluating the growth in these girls. Growth hormone (GH) has been used to accelerate growth and is known to increase adult height. Estrogen replacement treatment is also necessary for most girls with TS because of hypergonadotropic hypogonadism. Therefore, both GH therapy and estrogen replacement treatment are essential in girls with TS. An optimal treatment should be determined considering both GH treatment and age-appropriate induction of puberty. In this review, we discuss the growth in girls with TS, including overall growth, pubertal growth, the secular trend, growth-promoting treatment, and sex hormone replacement treatment.
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Hormona de Crecimiento Humana , Síndrome de Turner , Niño , Femenino , Humanos , Síndrome de Turner/complicaciones , Síndrome de Turner/tratamiento farmacológico , Hormona de Crecimiento Humana/uso terapéutico , Hormona del Crecimiento/uso terapéutico , Pubertad , Terapia de Reemplazo de HormonasRESUMEN
INTRODUCTION: Transient neonatal diabetes mellitus (TNDM) is a rare condition that is characterized by the presence of diabetes mellitus during the first 6 months of life and remission by 18 months of age. It usually relapses at a median age of 14 years. Hyperinsulinaemic hypoglycaemia is a relatively common complication during remission. Although ß-cell function is reported to be impaired at relapse, the clinical course of glycaemic profiles during remission in patients with TNDM remains largely unknown. CASE PRESENTATION: Longitudinal glycaemic profiles were investigated annually from remission (185 days) to relapse (14.5 years) in a patient with TNDM due to paternal 6q24 duplication using the oral glucose tolerance test (glucose intake: 1.75 g/kg to a maximum of 75 g). The patient's ß-cell function and insulin sensitivity were assessed by calculating the insulinogenic index, homeostasis model assessment of ß-cell function (HOMA-ß), homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index, and Matsuda index. Early insulin response to glucose intake was impaired throughout remission, whereas fasting insulin and ß-cell function by HOMA-ß gradually increased in the first few years since remission, followed by a gradual decline in function. In contrast, HOMA-IR fluctuated and peaked at 6.5 years of age. CONCLUSION: This is the first report of annual longitudinal glycaemic profiles in a patient with 6q24-related TNDM during remission. We identified fluctuations in ß-cell function and insulin resistance during remission.
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Glucemia/fisiología , Diabetes Mellitus/fisiopatología , Hiperinsulinismo , Resistencia a la Insulina , Adolescente , Glucemia/análisis , Diabetes Mellitus/congénito , Prueba de Tolerancia a la Glucosa , Humanos , Hiperinsulinismo/complicaciones , Lactante , Recién Nacido , Enfermedades del Recién Nacido , Masculino , Enfermedades Raras , Remisión EspontáneaRESUMEN
Cortical bone structure is a crucial determinant of bone strength, yet for many years studies of novel genes and cell signalling pathways regulating bone strength have focused on the control of trabecular bone mass. Here we focus on mechanisms responsible for cortical bone development, growth, and degeneration, and describe some recently described genetic-driven modifications in humans and mice that reveal how these processes may be controlled. We start with embryonic osteogenesis of preliminary bone structures preceding the cortex and describe how this structure consolidates then matures to a dense, vascularised cortex containing an increasing proportion of lamellar bone. These processes include modelling-induced, and load-dependent, asymmetric cortical expansion, which enables the cortex's transition from a highly porous woven structure to a consolidated and thickened highly mineralised lamellar bone structure, infiltrated by vascular channels. Sex-specific differences emerge during this process. With aging, the process of consolidation reverses: cortical pores enlarge, leading to greater cortical porosity, trabecularisation and loss of bone strength. Each process requires co-ordination between bone formation, bone mineralisation, vascularisation, and bone resorption, with a need for locational-, spatial- and cell-specific signalling pathways to mediate this co-ordination. We will discuss these processes, and a number of cell-signalling pathways identified in both murine and human genetic studies to regulate cortical bone mass, including signalling through gp130, STAT3, PTHR1, WNT16, NOTCH, NOTUM and sFRP4.
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Desarrollo Óseo/genética , Condrocitos/fisiología , Hueso Cortical/crecimiento & desarrollo , Osteoblastos/fisiología , Osteoclastos/fisiología , Osteocitos/fisiología , Animales , Hueso Cortical/fisiología , Humanos , Porosidad , Transducción de Señal/genéticaRESUMEN
Parathyroid hormone-related protein (PTHrP, gene name Pthlh) is a pleiotropic regulator of tissue homeostasis. In bone, Dmp1Cre-targeted PTHrP deletion in osteocytes causes osteopenia and impaired cortical strength. We report here that this outcome depends on parental genotype. In contrast to our previous report using mice bred from heterozygous (flox/wild type) Dmp1Cre.Pthlhf/w parents, adult (16-week-old and 26-week-old) flox/flox (f/f) Dmp1Cre.Pthlhf/f mice from homozygous parents (Dmp1Cre.Pthlhf/f(hom) ) have stronger bones, with 40% more trabecular bone mass and 30% greater femoral width than controls. This greater bone size was observed in Dmp1Cre.Pthlhf/f(hom) mice as early as 12 days of age, when greater bone width was also found in male and female Dmp1Cre.Pthlhf/f(hom) mice compared to controls, but not in gene-matched mice from heterozygous parents. This suggested a maternal influence on skeletal size prior to weaning. Although Dmp1Cre has previously been reported to cause gene recombination in mammary gland, milk PTHrP protein levels were normal. The wide-bone phenotype was also noted in utero: Dmp1Cre.Pthlhf/f(hom) embryonic femurs were more mineralized and wider than controls. Closer examination revealed that Dmp1Cre caused PTHrP recombination in placenta, and in the maternal-derived decidual layer that resides between the placenta and the uterus. Decidua from mothers of Dmp1Cre.Pthlhf/f(hom) mice also exhibited lower PTHrP levels by immunohistochemistry and were smaller than controls. We conclude that Dmp1Cre leads to gene recombination in decidua, and that decidual PTHrP might, through an influence on decidual cells, limit embryonic bone radial growth. This suggests a maternal-derived developmental origin of adult bone strength. © 2021 American Society for Bone and Mineral Research (ASBMR).
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Osteocitos , Proteína Relacionada con la Hormona Paratiroidea , Animales , Desarrollo Óseo/genética , Huesos , Decidua , Femenino , Masculino , Ratones , Proteína Relacionada con la Hormona Paratiroidea/genética , EmbarazoRESUMEN
BACKGROUND: Large changes in height standard deviation score (SDS) have been reported from birth to 3 years of age. We analyzed how early these changes start and whether they are affected by nutrition. METHODS: The longitudinal growth of 1,849 children born between March 1 2007 and August 31 2007 or between March 1, 2009 and August 31 2009 with five records from birth to 3 years of age was analyzed. RESULTS: The height SDS at birth was positively correlated with body mass index (BMI) SDS at birth (r = 0.224, P < 0.0001). The height SDS at birth decreased among children with a positive height SDS and increased among children with a negative height SDS. The changes occurred immediately after birth and became more modest as children aged. Regarding the change in the height SDS from birth to 3 years of age, 33.4% of children increased more than 0.5 SDs, 39.8% of children decreased more than 0.5 SDs, and 34.4% of children remained within ±0.5 SDs. The change in height SDS displayed a strong positive correlation with the change in weight during the four periods. From birth till 3 months, from 3 months till 6 months, from 6 months till 1.5 years, and from 1.5 years till 3 years. CONCLUSIONS: The significant positive correlation between height SDS and BMI SDS suggests an effect of children's nutrition status in utero. The height SDS change started immediately after birth and the change was largest from birth to 3 months. A positive correlation between changes in height SDS and weight suggest that growth during early childhood depends on nutritional status.
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Estatura , Estado Nutricional , Adulto , Índice de Masa Corporal , Niño , Preescolar , Humanos , Recién NacidoAsunto(s)
Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Proteínas de la Membrana/genética , Mutación , Fenotipo , Factores de Transcripción/genética , Autopsia , Preescolar , Análisis Mutacional de ADN , Resultado Fatal , Estudios de Asociación Genética/métodos , Pruebas Genéticas , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/genética , Humanos , Lactante , Radiografía Torácica , Evaluación de Síntomas , Síndrome , Anomalías Urogenitales/diagnóstico , Anomalías Urogenitales/genéticaRESUMEN
BACKGROUND: Many trace elements are essential for infant growth and development during early life. Their concentrations in breast milk vary depending on social and economic factors. Nonetheless, the present available values in Japan were derived from lactating mothers approximately 15 years ago. METHODS: Healthy mothers who gave birth to a single infant after 37 weeks of gestation at Teikyo University Hospital were recruited between July 2016 and December 2017. They were encouraged to collect breast milk samples and a self-administered food frequency questionnaire at 1 and 3 months postpartum. Anthropometric data for the mothers and their infants were also collected. Overall, 79 subjects were analyzed after excluding subjects with inadequate data in the food frequency questionnaire, insufficient breast milk samples, and medication that could affect dietary intakes. Trace element concentrations were determined by inductively coupled plasma mass spectrometry, and their correlation with several factors were investigated. RESULTS: Trace element concentrations were widely distributed as previously reported. Median concentrations of Cr, Mn, Fe, Cu, Zn, Se, and Mo were 0.8, 0.8, 98, 50, 272, 2.2, and 0.7 µg/dL at 1 month postpartum and 0.6, 0.7, 55, 33, 177, 2.1, and 0.7 µg/dL at 3 months postpartum, respectively. There were no correlations between trace element concentrations and either mothers' intakes or infants' growth. In contrast, there were significant correlations between several trace elements and macronutrients in addition to inter-element correlations among almost all trace elements. CONCLUSIONS: Trace element concentrations in mature breast milk were determined from recently lactating mothers in Japan.
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Oligoelementos , Femenino , Humanos , Lactante , Japón , Lactancia , Leche Humana/química , MadresRESUMEN
Nail-patella syndrome (NPS) is a multi-system disorder characterized by hypoplastic nails, hypoplastic patella, skeletal deformities, and iliac horns, which is caused by heterozygous variants of LMX1B. Nephropathy ranging from mild urinary abnormality to end-stage renal disease occurs in some individuals with NPS. Because of the low prevalence of NPS and the lack of longitudinal studies of its kidney involvement, the clinical, pathological, and genetic features characterizing severe nephropathy remain unclear. We conducted a Japanese survey of NPS with nephropathy, and analyzed their clinical course, pathological features, and factors associated with severe renal phenotype. LMX1B gene analysis and luciferase reporter assay were also performed. Among 13 NPS nephropathy cases with genetic validation, 5 patients who had moderate-to-massive proteinuria progressed to advanced chronic kidney disease or end-stage renal disease. Pathological findings in the early phase did not necessarily correlate with renal prognosis. Variants associated with deteriorated renal function including a novel variants were confined to the N-terminal region of the LIM domain and a short sequence in the LMX1B homeodomain, which were distinct from reported variants found in isolated nephropathy without extrarenal manifestation (LMX1B-associated nephropathy). Luciferase reporter analysis demonstrated that variants in patients with severe renal phenotype caused haploinsufficiency, but no dominant-negative effects on promoter activation. A distinct proportion of NPS nephropathy patients progressed to end-stage renal disease in adolescence or young adulthood. Patients with moderate or severe proteinuria, especially those with variants in specific regions of LMX1B, should be monitored for potential deterioration of renal function.
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Síndrome de la Uña-Rótula/genética , Nefritis Hereditaria/genética , Fenotipo , Proteinuria/genética , Adolescente , Animales , Células COS , Niño , Preescolar , Chlorocebus aethiops , Femenino , Humanos , Proteínas con Homeodominio LIM/genética , Proteínas con Homeodominio LIM/metabolismo , Masculino , Persona de Mediana Edad , Mutación , Síndrome de la Uña-Rótula/patología , Nefritis Hereditaria/patología , Regiones Promotoras Genéticas , Proteinuria/patología , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Bone strength is determined by its dense cortical shell, generated by unknown mechanisms. Here we use the Dmp1Cre:Socs3f/f mouse, with delayed cortical bone consolidation, to characterise cortical maturation and identify control signals. We show that cortical maturation requires a reduction in cortical porosity, and a transition from low to high density bone, which continues even after cortical shape is established. Both processes were delayed in Dmp1Cre:Socs3f/f mice. SOCS3 (suppressor of cytokine signalling 3) inhibits signalling by leptin, G-CSF, and IL-6 family cytokines (gp130). In Dmp1Cre:Socs3f/f bone, STAT3 phosphorylation was prolonged in response to gp130-signalling cytokines, but not G-CSF or leptin. Deletion of gp130 in Dmp1Cre:Socs3f/f mice suppressed STAT3 phosphorylation in osteocytes and osteoclastic resorption within cortical bone, leading to rescue of the corticalisation defect, and restoration of compromised bone strength. We conclude that cortical bone development includes both pore closure and accumulation of high density bone, and that these processes require suppression of gp130-STAT3 signalling in osteocytes.
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Desarrollo Óseo , Receptor gp130 de Citocinas/metabolismo , Osteocitos/citología , Osteocitos/metabolismo , Factor de Transcripción STAT3/metabolismo , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo , Animales , Huesos/metabolismo , Receptor gp130 de Citocinas/genética , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Factor de Transcripción STAT3/genética , Transducción de Señal , Proteína 3 Supresora de la Señalización de Citocinas/genéticaRESUMEN
Background Hereditary vitamin D-resistant rickets (HVDRR) is caused by vitamin D receptor (VDR) defects. Patients with HVDRR do not respond to standard doses of calcitriol and oral calcium (Ca) treatment and need to be treated with intravenous Ca (IV-Ca) via a central route. However, central catheter-related complications can cause significant morbidity. Case presentation Four unrelated patients with HVDRR presenting with rickets and alopecia totalis were administered intermittent IV-Ca treatment (2-5 times/week) through a peripheral route. No complications such as infection, extravasation or arrhythmias were detected upon peripheral infusion. Peripheral 1-22 months' duration of IV-Ca normalized parathyroid hormone (PTH) and alkaline phosphatase (ALP) in all patients, after which, oral Ca of 200-400 mg/kg/day and calcitriol of 0.5 µg/kg/day were sufficient to maintain normal PTH levels. Molecular studies on the VDR gene showed a previously reported homozygous c.454C > T (p.Q152*) pathogenic variant in two patients. Two novel homozygous variants in the other two patients were detected: (1) c.756-2A > G, which affects the splice acceptor site, and (2) c.66dupG (p.I23Dfs*20) variant leading to a frameshift that results in a premature stop codon. Conclusions Peripheral IV-Ca treatment is an effective and practical alternative treatment mode that provides dramatic clinical benefit in patients with HVDRR.
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Hormonas y Agentes Reguladores de Calcio/administración & dosificación , Calcio/administración & dosificación , Raquitismo Hipofosfatémico Familiar/tratamiento farmacológico , Raquitismo Hipofosfatémico Familiar/patología , Mutación , Receptores de Calcitriol/genética , Niño , Preescolar , Raquitismo Hipofosfatémico Familiar/genética , Femenino , Humanos , Lactante , Masculino , PronósticoRESUMEN
Childhood obesity affects both pubertal growth and pubertal timing. We evaluated pubertal timing-mediated effects of childhood obesity on pubertal growth. This retrospective, representative-population-based cohort study included 6,733 boys and 6,916 girls born between April 1975 and March 1976 in Akita Prefecture, Japan. Individual changes in height standard deviation score between 7 and 17 years (ΔHtSDS), body mass index Z-score at 7 years (BMIZ), and estimated age at peak height velocity (ÂPHV) were used as surrogate indicators of pubertal growth, childhood obesity and pubertal timing, respectively. ÂPHV-mediated effect of BMIZ on ΔHtSDS was evaluated, and non-ÂPHV-mediated effect was calculated. Based on BMIZ, participants were categorized into three groups (underweight, normal-weight and obese groups), and the differences in ΔHtSDS between obese and normal-weight or underweight groups and ratios of non-ÂPHV-mediated effect were determined. ΔHtSDS values in the obese group were lower by 1.23 in boys and 1.17 in girls than those in the underweight group and by 0.87 in boys and 0.85 in girls than those in the normal-weight group. Non-ÂPHV-mediated effect on the reduced ΔHtSDS in the obese group compared to the underweight and normal-weight groups accounted for 68% and 71% in boys and 59% and 64% in girls, respectively. Thus, childhood obesity is associated with reduced pubertal growth regardless of pubertal timing. This reduced pubertal growth observed in children with obesity could be more affected by non-pubertal timing-mediated effect rather than pubertal timing-mediated effect.
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Estatura , Obesidad Infantil/fisiopatología , Pubertad , Adolescente , Factores de Edad , Estudios de Casos y Controles , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Factores Sexuales , Delgadez/fisiopatologíaRESUMEN
BACKGROUND: The precise mechanism of hyponatremia in Kawasaki disease (KD) remains elusive because assessment of volume status based on serial changes in body weight is lacking in previous reports. METHODS: Seventeen patients who were diagnosed with KD and hyponatremia (serum sodium levels <135 mmol/L) were analyzed. Volume status was assessed based on serial changes in body weight. Plasma arginine vasopressin (ADH), urine electrolytes, and serum cytokine levels were measured on diagnosis of hyponatremia. An increase in body weight by >3% was defined as hypervolemia and a decrease in body weight by >3% was defined as hypovolemia. RESULTS: The volume status was hypervolemic in three patients (18%), euvolemic in 14 (82%), and hypovolemic in none (0%). Five (29%) patients were diagnosed with "syndrome of inappropriate secretion of antidiuretic hormone" (SIADH) and no patients were diagnosed with hypotonic dehydration. The contribution of decreased total exchangeable cations (salt loss) to hyponatremia (5.9% [interquartile range, 4.3%, 6.7%]) was significantly larger than that of increased total body water (-0.7% [-1.8%, 3.1%]) (P = 0.004). Serum interleukin-6 levels were elevated in all of the nine patients who were evaluated. Among the 12 (71%) patients who did not meet the criteria of SIADH and hypotonic dehydration, plasma ADH levels were inappropriately high in ten patients. These patients were also characterized by euvolemic or hypervolemic hyponatremia and salt loss, which might be compatible with a diagnosis of SIADH. CONCLUSIONS: Our study shows that hyponatremia in KD is euvolemic or hypervolemic and is associated with nonosmotic secretion of ADH and salt loss in the majority of patients.