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Metabolic syndrome (MetS) is defined as a cluster of alterations related with insulin resistance (obesity, dyslipidemia, hypertension, and impaired glucose metabolism), which are associated with a higher risk of cardiovascular disease in adults. Several definitions have been proposed for older children and adolescents. However, no definitions have been made in accordance with pubertal status, and those in prepubertal state have not received attention enough, despite there are data suggesting the early presence of risk factors. The new insights concerning healthy and unhealthy metabolic status or the addition of novel metabolic risk biomarkers, may contribute to the knowledge about the development of MetS in children. This manuscript reviews the available evidence on MetS during childhood, focusing on the prepubertal period.

Encephalomyopathic mitochondrial DNA (mtDNA) depletion syndrome 13 (MTDPS13) is a rare genetic disorder caused by defects in F-box leucine-rich repeat protein 4 (FBXL4). Although FBXL4 is essential for the bioenergetic homeostasis of the cell, the precise role of the protein remains unknown. In this study, we report two cases of unrelated patients presenting in the neonatal period with hyperlactacidemia and generalized hypotonia. Severe mtDNA depletion was detected in muscle biopsy in both patients. Genetic analysis showed one patient as having in compound heterozygosis a splice site variant c.858+5G>C and a missense variant c.1510T>C (p.Cys504Arg) in FBXL4. The second patient harbored a frameshift novel variant c.851delC (p.Pro284LeufsTer7) in homozygosis. To validate the pathogenicity of these variants, molecular and biochemical analyses were performed using skin-derived fibroblasts. We observed that the mtDNA depletion was less severe in fibroblasts than in muscle. Interestingly, the cells harboring a nonsense variant in homozygosis showed normal mtDNA copy number. Both patient fibroblasts, however, demonstrated reduced mitochondrial transcript quantity leading to diminished steady state levels of respiratory complex subunits, decreased respiratory complex IV (CIV) activity, and finally, low mitochondrial ATP levels. Both patients also revealed citrate synthase deficiency. Genetic complementation assays established that the deficient phenotype was rescued by the canonical version of FBXL4, confirming the pathological nature of the variants. Further analysis of fibroblasts allowed to establish that increased mitochondrial mass, mitochondrial fragmentation, and augmented autophagy are associated with FBXL4 deficiency in cells, but are probably secondary to a primary metabolic defect affecting oxidative phosphorylation.

Molecular diagnosis is a useful diagnostic tool in primary nephrogenic diabetes insipidus (NDI), an inherited disease characterized by renal inability to concentrate urine. The AVPR2 and AQP2 genes were screened for mutations in a cohort of 25 patients with clinical diagnosis of NDI. Patients presented with dehydration, polyuria-polydipsia, failure to thrive (mean ± SD; Z-height -1.9 ± 2.1 and Z-weight -2.4 ± 1.7), severe hypernatremia (mean ± SD; Na 150 ± 10 mEq/L), increased plasma osmolality (mean ± SD; 311 ± 18 mOsm/Kg), but normal glomerular filtration rate. Genetic diagnosis revealed that 24 male patients were hemizygous for 17 different putative disease-causing mutations in the AVPR2 gene (each one in a different family). Of those, nine had not been previously reported, and eight were recurrent. Moreover, we found those same AVPR2 changes in 12 relatives who were heterozygous carriers. Further, in one female patient, AVPR2 gene study turned out to be negative and she was found to be homozygous for the novel AQP2 p.Ala86Val alteration.Genetic analysis presumably confirmed the diagnosis of nephrogenic diabetes insipidus in every patient of the studied cohort. We emphasize that we detected a high presence (50 %) of heterozygous females with clinical NDI symptoms.• In most cases (90 %), inherited nephrogenic diabetes insipidus (NDI) is an X-linked disease, caused by mutations in the AVPR2 gene. • In rare occasions (10 %), it is caused by mutations in the AQP2 gene. What is new: • In this study, we report 10 novel mutations associated with NDI. • We have detected a high presence (50 %) of heterozygous carriers with clinical NDI symptoms.

IntroductionHypertension is a public health problem and its prevalence in children is on the rise, often continuing into adulthood and increasing the risk related cardiovascular complications. Sleep plays an essential role in childrenu2019s growth and several studies suggest that insufficient sleep duration is associated with hypertension in adults. However, few studies have evaluated this association in children. Thus, the aim of the study is to ascertain whether the sleep duration is a risk factor for elevated blood pressure (BP) in children.MethodsWe studied 776 children (5-18 years old), (46.7% male, 78.8% 5-13 years, 73.6% overweight/obesity). Weight and height were measured and body mass index (BMI) was calculated. BP was measured with an electronic manometer to find a 25.3% of children with an elevated systolic BP (SBP, >P90th) and 14% with an elevated diastolic BP (DBP, >P90th) (Task Force 2017). Sleep duration was assessed by asking the parents u201cu00bfHow many hours does your child sleep in a typical weekday?u201d. Weekday sleep hours were considered since they are more representative of childrenu2019s routines than weekend hours. Hours were converted into a dichotomous variable based on the fulfillment or not of the u201cCanadian 24-Hour Movement Guidelines for Children and Youth recommendationsu201d: 9-11 hours for 5- to 13-year-olds; 8-10 hours for 14- to 17-year-olds. A spearman correlation analysis was performed between sleep duration, SBP and DBP. Then, a general linear model analysis adjusted for BMI Z-score was done to evaluate differences in SBP and DBP between children following the sleep recommendations. Analyses were stratified by sex and age range (5-13 and 14-17). ResultsIn girls 5-13 years, we found a significant negative correlation between sleep duration and body mass index (BMI) (r=-0.226, p=0.000) and between sleep and systolic BP (r=-0.188, p=0.001). Girls 5-13 years not following sleep recommendations showed significantly higher SBP values than those who followed the recommendations (112u00b111 mmHg vs. 106u00b112 mmHg, p=0.007), independently of BMI. No significant differences were observed in girls 14-17 years nor in males.DiscussionIn the present study, we show that girls 5-13 years with shorter sleep duration show increased SBP values independently of BMI, in contrast to previous studies which showed similar associations that disappeared when adjusting for BMI. Our results support the need for wider strategies in population education so that sleep recommendations are followed by children in the general population.

Los objetivos de este estudio son, realizar una descrip-ción de las características demográficas, antropométricas y de las alteraciones metabólicas de niños atendidos por obe-sidad resaltando las características aquellos casos de obesidad de inicio temprano (< 10 años) y los de inicio precoz (< 5 años), y evaluar la capacidad diagnóstica de la definición de síndrome metabólico (SM) según diferentes criterios. Métodos: Es un estudio retrospectivo, caso-control, trans-versal, multicéntrico. Han participado un total de 10 Uni-dades de Endocrinología Pediátrica de diferentes hospitales españoles con un grupo de 469 niños con obesidad de inicio temprano y otro grupo de 30 niños con obesidad de inicio precoz. El grupo control estuvo constituido por 224 niños sanos menores de 10 años. Se realizó una valoración antro-pométrica y determinación analítica de parámetros del me-tabolismo de los hidratos de carbono y lipidograma. Resultados: La presencia de alteraciones metabólicas asociadas a la obesidad en la etapa infanto-juvenil en Espa-ña es notable, de forma aislada, o englobada bajo la defini-ción de SM. La prevalencia de éste aumenta sustancialmen-te cuando se considera la resistencia periférica a la acción de la insulina como criterio diagnóstico. Se demuestra cómo en niños menores de 10 años, dichas alteraciones están presen-tes en un porcentaje reseñable, y se encuentran las primeras alteraciones metabólicas ya en niños obesos < 5 años. Conclusión: En los niños españoles existen alteracio-nes metabólicas asociadas a la obesidad en la etapa in-fanto-juvenil de forma aislada o englobada bajo la de-finición de SM, y ya están presentes a edades precoces. The objectives of this study are to provide a description of the demographic, anthropometric characteristics and metabolic abnormalities in children with early-onset (< 10 years) and of very-early-onset obesity (< 5 years). We also evaluate the diagnostic ability using the definition of meta-bolic syndrome (MS) according to different criteria. Methods: It is a retrospective, case-control, cross-sec-tional, multicenter study. A total of 10 Pediatric Endo-crinology Units in different Spanish hospitals were in-volved. A group of 469 children with early-onset obesity and another group of 30 children with very early-onset obesity were studied. The control group consisted of 224 healthy children younger than 10 years. Anthropometric and analytical determination of carbohydrates metabo-lism parameters and the lipid profile were performed. Results: The presence of metabolic alterations associa-ted with obesity in children and adolescents in Spain is remarkable, either on their own, or encompassed within the definition of MS. This prevalence increases substan-tially when considering the peripheral resistance to in-sulin action as a diagnostic criterion. It also shows how children who could not be diagnosed with MS according to the definition provided by the International Diabetes Federation (IDF) due to age below 10 years, these altera-tions are already present in a remarkable percentage. In fact, metabolic abnormalities are already present in the very-early-onset obese children (

Antecedentes: Los niveles adecuados de vitamina D y calcio en la infancia determinan el desarrollo adecuado de la masa ósea. En la actualidad se ha detectado déficit de vitamina D en determinadas poblaciones infantojuveniles, como en lactantes y adolescentes pero existe información insuficiente respecto al estado de la vitamina D en niños de otras edades. Objetivo: Determinar los niveles séricos de vitamina D en niñas prepuberales sanas de una ciudad del sur de Europa y estudiar el efecto de la exposición solar, la actividad física y la ingesta. Métodos: Se estudiaron 56 niñas caucasianas, sanas y prepúberes entre 7-10 años. Se recogieron datos sobre ingesta nutricional y actividad física. Las muestras de sangre se obtuvieron en diciembre. Resultados: La ingesta de vitamina D fue significativamente menor a las recomendaciones internacionales. Los niveles medios de calcidiol fueron de 40,07 ± 10,49 ng/ ml. Ninguna niña presentó un nivel inferior a 20 ng/ml; un 25% (14 niñas) tenían unos niveles entre 20-30 ng/ml, y un 75 % superiores a 30 ng/ml. No hemos encontrado diferencias en los niveles de vitamina D entre las niñas que realizaban actividad física, y las sedentarias. Conclusión: Los niveles de vitamina D en niñas prepúberes que viven al sur de España al inicio del invierno son adecuados. No obstante, se debe asegurar una ingesta adecuada de vitamina D, así como una exposición solar suficiente y realizar seguimiento en estas edades para evitar deficiencias. Background: Vitamin D and calcium play an important role in peak bone mass acquisition. Recent studies have suggested that vitamin D deficiency in children is widespread, mainly during infancy and adolescent years. However, the vitamin D status at others ages is unsufficiently investigated. Objectives: To determine the vitamin D status in prepubertal, healthy South European girls, and to examine the relationship between serum vitamin D concentrations, sun exposure, physical activity and dietary intake. Methods: A cross-sectional observational study was conducted on 56 Caucasian; healthy and prepubertal girls aged 7-10 years. Dietary information, amount of sunlight exposure and activity were estimated. Blood samples were extracted in the first week of December. Results: Vitamin D intake was below the international recommended references. Mean serum vitamin D was 40.07 ± 10.49 ng/ml. No girl presented a level lower than 20 ng/ml; 25% had levels between 20-30 ng/ml and 75% above 30 ng/ml. We have not found differences in vitamin D levels from the girls who did sport and those who were sedentary. Conclusions: Vitamin D status is suitable for prepubertal girls living in the South of Spain at the beginning of winter. However, it is necessary to follow-up girls and check and adequate vitamin D intake, as well as sufficient sun exposure.

Background: In 2007, the Hospital Infantil Los Ángeles (HILA) in Colombia implemented a slightly-modified version of the WHO guidelines for the diagnosis and management of malnutrition during childhood. Objective: To evaluate the efficacy of the WHO-HILA protocol in children hospitalized with severe, chronic marasmus and kwashiorkor malnutrition (MS-KWK) in 2007 and 2008. Material and methods: In this descriptive retrospective study the records of 100 children hospitalized with MSKWK were initially evaluated. Of these, 30 fulfilled the inclusion criteria: children of both sexes with a primary diagnosis of MS-KWK. Patients with any chronic disease liable to cause malnutrition were excluded. Anthropometric parameters, clinical signs and biochemical indicators of malnutrition were assessed upon admission and again at discharge following application of the WHO guidelines. Univariate analysis was performed for each study variable; serum hemoglobin and albumin levels on admission and at discharge were compared, and data were subjected to bivariate analysis. Results: Marasmus was diagnosed in 23.3% of children, kwashiorkor in 73.3% and marasmic kwashiorkor in 3.3%. The major clinical findings were: edema (70%), emaciation (40%), "flag sign" hair (42.86%), low serum albumin (93%) and anemia (80%). Thirteen children following the WHO-HILA protocol showed a significant nutritional status improvement (p < 0.05), whereas no improvement was noted in the 17 children not treated according to the protocol. Conclusions: Application of the WHO-HILA protocol was associated with reduced morbimortality in children with marasmus-kwashiorkor malnutrition. Implementation of this protocol should therefore be considered in all children´s hospitals in countries where this disease is prevalent. Introducción: En 2007, el Hospital Infantil de Los Ángeles (HILA) en Colombia implementó una versión del protocolo-OMS para el diagnóstico y tratamiento de la malnutrición en la infancia. Objetivo: Evaluar la aplicación del protocolo de la OMS-HILA en niños hospitalizados con marasmo y/o kwashiorkor (MS-KWK) durante 2007-2008. Material y métodos: En este estudio retrospectivo, se evaluaron 100 niños hospitalizados con MS-KWK; 30 cumplieron los criterios de inclusión: niños de ambos sexos con MS-KWK primario. Los pacientes con enfermedades crónicas que pudieran causar desnutrición fueron excluidos. Se evaluaron determinados parámetros antropométricos, y signos clínicos y bioquímicos de desnutrición según el protocolo de la OMS, al ingreso y al alta. Se realizó un análisis univariante; los niveles de hemoglobina y albúmina séricas fueron comparados al ingreso y al alta, y los datos fueron sometidos a análisis de dos variables. Resultados: Se diagnosticaron de marasmo al 23,3% de los niños, de kwashiorkor al 73,3% y de kwashiorkor marásmico al 3,3%. Los hallazgos clínicos más importantes fueron: edema (70%), emaciación (40%), "signo de bandera" (42,86%), albúmina baja (93%) y anemia (80%). Trece niños mostraron mejoría significativa del estado nutricional tras aplicar el protocolo OMS-HILA (p < 0,05), mientras que no ocurrió en 17 niños no tratados según el protocolo. Conclusiones: La aplicación del protocolo de la OMSHILA se asoció con una reducción de la morbimortalidad en los niños con desnutrición marasmo-kwashiorkor. La aplicación completa y continuada de este protocolo debe ser considerada en los hospitales infantiles de todos los países donde esta enfermedad es prevalente.

Elevated plasma uric acid levels are associated with obesity and could be an expression of insulin-resistant state. The aim of the present study was to evaluate plasma uric acid in obese and normal-weight children exclusively at prepubertal stage and its relationship with anthropometric measurements, intake, and features of the insulin resistance syndrome. A study was performed in 34 obese and 20 normal-weight prepubertal children. Nutrient intake was determined using a 72 h recall questionnaire and a consumption food frequency questionnaire. Anthropometric parameters and fasting plasma lipids, glucose, insulin, leptin, adiponectin, tumour necrosis factor (TNF-α) and uric acid were measured. Multiple regression analysis was used to identify association of anthropometric parameters, nutrient intake and insulin resistance syndrome variables (arterial blood pressure, plasma glucose, insulin, homeostasis model assessment of insulin resistance index- HOMA- triacylglycerols and, HDL-cholesterol) with uric acid. Plasma uric concentration was significantly higher in the obese group than in the control group and when adjusted by sex, age and BMI was positively associated with tricipital skinfold and insulin resistance, and negatively with adiponectin. In multiple regression analysis, BMI, HDL-cholesterol and adiponectin were independent predictors of plasma uric acid. In conclusion, elevated levels of uric acid in obese children, compared with lean subjects, at the prepubertal period, seems to be an early metabolic alteration that is associated with other features of insulin resistance syndrome. Los niveles elevados de ácido úrico plasmáticos se asocian a la obesidad y pueden ser la expresión de un estado de resistencia insulínica. El objetivo de este estudio ha sido evaluar la concentración plasmática de ácido úrico en niños obesos y normales, exclusivamente en edad prepuberal, y determinar su relación con las medidas antropométricas, la ingesta dietética y los parámetros asociados al síndrome de resistencia insulínica. El estudio se llevó a cabo en 34 niños obesos y 20 controles en edad prepuberal a los cuales se les estimó su ingesta dietética mediante el registro de un cuestionario de ingesta de alimentos de 72 h y un cuestionario de frecuencia de consumo de alimentos y se determinaron, además de los parámetros antropométricos, la glucosa, la insulina, la leptina, la adiponectina y el factor de necrosis tumoral alfa (TNF-α) plasmáticos. Se realizó un análisis de regresión múltiple para identificar la asociación entre los niveles de ácido úrico y los parámetros antropométricos, la ingesta de nutrientes y las variables clásicas relacionadas con el síndrome de resistencia insulínica (hipertensión, glucosa, insulina, índice de resistencia insulínica HOMA, triglicéridos y HDL-colesterol plasmáticos), así como con leptina, adiponectina y TNF-α. La concentración plasmática de ácido úrico fue significativamente más elevada en los niños obesos que en los controles y, cuando se ajustó por sexo, edad e índice de masa corporal, los niveles de ácido úrico se asociaron con el pliegue tricipital y la resistencia inulínica, y negativamente con la adiponectina. En el análisis de regresión múltiple, el índice de masa corporal, el HDL-colesterol y la adiponectina fueron predictores independientes del ácido úrico plasmático. En conclusión, los niveles elevados de ácido úrico en niños obesos en edad prepuberal, comparado con los de los niños normales, representan una alteración metabólica temprana asociada con la resistencia insulínica.