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Abstract Background Identifying children and adolescents with cardiometabolic risk at an early stage is crucial for effective treatment and prevention. From a practical perspective, this could be accomplished by assessing the presence of abdominal obesity, which serves as a surrogate indicator of increased cardiometabolic risk and is easy to measure. However, the assessment of abdominal obesity via waist circumference has not yet become a standard procedure in pediatric healthcare. The present study aimed to analyze the secular trends in increased cardiometabolic risk, as indicated by waist circumference among Spanish children and adolescents. Methods This study included 4861 children and adolescents aged 8 to 16 years from two nationwide representative cross-sectional surveys, the EnKid study and the PASOS study, conducted in 1998–2000 and 2019–2020, respectively. Anthropometric variables were measured in both surveys by trained personnel. Three different waist-to-height (WHtR) cutoffs were used to define abdominal obesity as criteria for cardiometabolic risk. BMI categories were defined according to the IOTF and WHO growth charts. Results Abdominal obesity [waist to height ratio (cm/cm) > 0.49] significantly increased from 40.7 to 56.1% and 93.8 to 97.2% in participants with overweight and obesity, respectively, between 1998–2000 and 2019–2020 (p

Abstract Background Oral cholic acid therapy is an effective therapy in children with primary bile acid synthesis deficiencies. Most reported patients with this treatment have 3β-hydroxy-Δ5-C27-steroid oxidoreductase deficiency. The aim of the study was the evaluation of cholic acid therapy in a cohort of patients with the rarer Δ4-3-oxosteroid 5β-reductase (Δ4-3-oxo-R) deficiency. Methods Sixteen patients with Δ4-3-oxo-R deficiency confirmed by AKR1D1 gene sequencing who received oral cholic acid were retrospectively analyzed. Results First symptoms were reported early in life (median 2 months of age), with 14 and 3 patients having cholestatic jaundice and severe bleeding respectively. Fifteen patients received ursodeoxycholic acid before diagnosis, with partial improvement in 8 patients. Four patients had liver failure at the time of cholic acid initiation. All 16 patients received cholic acid from a median age of 8.1 months (range 3.1–159) and serum liver tests normalized in all within 6–12 months of treatment. After a median cholic acid therapy of 4.5 years (range 1.1–24), all patients were alive with their native liver. Median daily cholic acid dose at last follow-up was 8.3 mg/kg of body weight. All patients, but one, had normal physical examination and all had normal serum liver tests. Fibrosis, evaluated using liver biopsy (n = 4) or liver elastography (n = 9), had stabilized or improved. Cholic acid therapy enabled a 12-fold decrease of 3-oxo-∆4 derivatives in urine. Patients had normal growth and quality of life. The treatment was well tolerated without serious adverse events and signs of hepatotoxicity. Conclusions Oral cholic acid therapy is a safe and effective treatment for patients with Δ4-3-oxo-R deficiency.

Treatment of fatty acid oxidation disorders is based on dietary, pharmacological and metabolic decompensation measures. It is essential to provide the patient with sufficient glucose to prevent lipolysis and to avoid the use of fatty acids as fuel as far as possible. Dietary management consists of preventing periods of fasting and restricting fat intake by increasing carbohydrate intake, while maintaining an adequate and uninterrupted caloric intake. In long-chain deficits, long-chain triglyceride restriction should be 10% of total energy, with linoleic acid and linolenic acid intake of 3–4% and 0.5–1% (5/1–10/1 ratio), with medium-chain triglyceride supplementation at 10–25% of total energy (total MCT+LCT ratio = 20–35%). Trihepatnoin is a new therapeutic option with a good safety and efficacy profile. Patients at risk of rhabdomyolysis should ingest MCT or carbohydrates or a combination of both 20 min before exercise. In medium- and short-chain deficits, dietary modifications are not advised (except during exacerbations), with MCT contraindicated and slow sugars recommended 20 min before any significant physical exertion. Parents should be alerted to the need to increase the amount and frequency of carbohydrate intake in stressful situations. The main measure in emergency hospital treatment is the administration of IV glucose. The use of carnitine remains controversial and new therapeutic options are under investigation.

Introduction: The prevalence of malnutrition among infants with congenital heart disease (CHD) is high. Early nutritional assessment and intervention contribute significantly to its treatment and improve outcomes. Our objective was to develop a consensus document for the nutritional assessment and management of infants with CHD. Material and methods: We employed a modified Delphi technique. Based on the literature and clinical experience, a scientific committee prepared a list of statements that addressed the referral to paediatric nutrition units (PNUs), assessment, and nutritional management of infants with CHD. Specialists in paediatric cardiology and paediatric gastroenterology and nutrition evaluated the questionnaire in 2 rounds. Results: Thirty-two specialists participated. After two evaluation rounds, a consensus was reached for 150 out of 185 items (81%). Cardiac pathologies associated with a low and high nutritional risk and associated cardiac or extracardiac factors that carry a high nutritional risk were identified. The committee developed recommendations for assessment and follow-up by nutrition units and for the calculation of nutritional requirements, the type of nutrition and the route of administration. Particular attention was devoted to the need for intensive nutrition therapy in the preoperative period, the follow-up by the PNU during the postoperative period of patients who required preoperative nutritional care, and reassessment by the cardiologist in the case nutrition goals are not achieved. Conclusions: These recommendations can be helpful for the early detection and referral of vulnerable patients, their evaluation and nutritional management and improving the prognosis of their CHD. Resumen: Introducción: La tasa de desnutrición entre los lactantes con cardiopatías congénitas (CC) es elevada. Una evaluación e intervención nutricional tempranas ayudan a su tratamiento y mejoran el pronóstico. El objetivo fue elaborar un documento de consenso para la evaluación y el tratamiento nutricional del lactante con CC. Material y Métodos: Se utilizó una técnica Delphi modificada. En base a la literatura y a su experiencia clínica, un comité científico elaboró un listado de afirmaciones que abordaban la derivación a Unidades de Nutrición Pediátrica (UNP), la evaluación y el manejo nutricional de los lactantes con CC. Especialistas en cardiología pediátrica, y gastroenterología y nutrición pediátrica evaluaron el cuestionario en 2 rondas. Resultados: Participaron 32 especialistas. Tras dos rondas de evaluación, se consensuaron 150 de 185 ítems (81%). Se determinaron patologías cardiacas de bajo y alto riesgo nutricional y factores asociados cardíacos o extracardíacos que confieren riesgo nutricional alto. Se elaboraron recomendaciones para la evaluación y seguimiento en unidades de nutrición y sobre el cálculo de los requerimientos nutricionales, el tipo de nutrición y la vía de administración. Se enfatiza la necesidad de un tratamiento nutricional intensivo en el preoperatorio, del seguimiento por la UNP en el postoperatorio cuando se haya necesitado intervención preoperatoria, y de la reevaluación por el cardiólogo cuando no se alcancen los objetivos nutricionales. Conclusiones: Estas recomendaciones pueden ser de ayuda para la detección precoz y derivación temprana de población vulnerable, su evaluación y tratamiento nutricional y para mejorar el pronóstico de su CC.

Hyperhomocysteinemia (HHcy) is recognized as an independent risk factor for various significant medical conditions, yet controversy persists around its assessment and management. The diagnosis of disorders afffecting homocysteine (Hcy) metabolism faces delays due to insufficient awareness of its clinical presentation and unique biochemical characteristics. In cases of arterial or venous thrombotic vascular events, particularly with other comorbidities, it is crucial to consider moderate to severe HHcy. A nutritional approach to HHcy management involves implementing dietary strategies and targeted supplementation, emphasizing key nutrients like vitamin B6, B12, and folate that are crucial for Hcy conversion. Adequate intake of these vitamins, along with betaine supplementation, supports Hcy remethylation. Lifestyle modifications, such as smoking cessation and regular physical activity, complement the nutritional approach to enhance Hcy metabolism. For individuals with HHcy, maintaining a plasma Hcy concentration below 50 μmol/L consistently is vital to lowering the risk of vascular events. Collaboration with healthcare professionals and dietitians is essential for developing personalized dietary plans addressing the specific needs and underlying health conditions. This integrated approach aims to optimize metabolic processes and reduce the associated health risks.

El tránsito al empleo competitivo de las personas con discapacidad intelectual en Canarias presenta carencias; de ahí que se esté implementando el programa de Empleo con Apoyo (EcA). Este es un modelo de inclusión laboral para personas con discapacidades significativas, basado en el acompañamiento y apoyo a la persona para facilitar su acceso al empleo. Dicho acompañamiento y apoyo es proporcionado por la figura del preparador laboral. Nuestro estudio pretende conocer: 1) la importancia del preparador laboral desde el punto de vista de los profesionales de los servicios de Empleo con Apoyo; 2) el papel de la formación profesional previa de los sujetos en el éxito de la inclusión. Se realizó un estudio cualitativo con profesionales, vinculados a programas de Empleo con Apoyo en Canarias, empleándose la técnica del grupo de discusión. Los resultados señalan que: 1) el preparador laboral es clave para el éxito de la inserción laboral, siendo importante el apoyo que proporciona a la persona y a la empresa; 2) el entrenamiento en competencias laborales básicas, previo a la inserción laboral, puede estar relacionado con el éxito en el empleo y también la “formación a la carta”. Se discute el papel del modelo como alternativa para garantizar el derecho a la inclusión sociolaboral de las personas con discapacidad intelectual.

Resumen: Introducción y objetivos: El objetivo primario fue explorar la tendencia epidemiológica de la enfermedad intestinal inflamatoria pediátrica en América Latina; los secundarios, obtener una visión general del enfoque diagnóstico/terapéutico de miembros de la SLAGHNP y explorar la relación entre la frecuencia de casos y los años del período evaluado. Material y métodos: Se realizó una encuesta en línea a pediatras gastroenterólogos de América Latina con la plataforma SurveyMonkey. Se preguntó la frecuencia anual de pacientes nuevos de 2005 a 2016, su variedad, los segmentos del tubo digestivo afectados, los métodos de diagnóstico y el tratamiento utilizado. Se evaluó la correlación entre la frecuencia anual y los años de estudio. Resultados: Se estudió a 607 pacientes; el diagnóstico de colitis ulcerativa se realizó en 475 (78.3%), de enfermedad de Crohn en 104 (17.1%) y de enfermedad intestinal inflamatoria no clasificable en 28 (4.6%). La tendencia de colitis ulcerativa tuvo un incremento lineal con coeficiente de correlación significativo entre la frecuencia de casos nuevos y el año de estudio; 67.6% tuvieron pancolitis. Los métodos de diagnóstico incluyeron datos clínicos, endoscopia y biopsias en más del 99% de los casos; los estudios de imagen se indicaron de manera selectiva. Los esquemas farmacológicos se circunscribieron a derivados del ácido 5-aminosalicílico, azatioprina, 6-mercaptopurina, infliximab y adalimumab. Conclusiones: La enfermedad intestinal inflamatoria pediátrica en América Latina parece incrementarse en el período estudiado con predominio de formas moderadas o graves de colitis ulcerativa; esta tendencia lineal puede indicar la posibilidad predictiva de incremento gradual en la próxima década, lo que es probable que tenga implicaciones epidemiológicas y clínicas. Abstract: Introduction and objectives: The primary aim was to explore the epidemiologic trend of pediatric inflammatory bowel disease in Latin America, and the secondary aims were to obtain an overview of the diagnostic/therapeutic focus of the members of the LASPGHAN and examine the relation of case frequency to year, during the study period. Materials and methods: Latin American pediatric gastroenterologists participated in an online survey, conducted through the SurveyMonkey platform, that investigated the yearly frequency of new inflammatory bowel disease patients within the time frame of 2005 to 2016, their disease variety, the gastrointestinal segments affected, and the diagnostic and treatment methods utilized. The correlation of new case frequency with each study year was evaluated. Results: A total of 607 patients were studied. The diagnoses were ulcerative colitis in 475 (78.3%) cases, Crohn's disease in 104 (17.1%), and inflammatory bowel disease D unclassified in 28 (4.6%). The trend in ulcerative colitis was a lineal increase in the frequency of new cases related to each study year, with a significant correlation coefficient. Pancolitis was found in 67.6% of the patients. The diagnostic methods included clinical data, endoscopy, and biopsies in more than 99% of the cases, and imaging studies were indicated selectively. Drug regimens were limited to 5-aminosalicylic acid derivatives, azathioprine, 6-mercaptopurine, infliximab, and adalimumab. Conclusions: Pediatric inflammatory bowel disease in Latin America appears to have increased during the years included in the study period, with a predominance of moderate or severe ulcerative colitis. That lineal trend suggests the predictive likelihood of a gradual increase in the coming years, with possible epidemiologic and clinical implications.

Introduction and aims: The primary aim was to explore the epidemiologic trend of pediatric inflammatory bowel disease in Latin America, and the secondary aims were to obtain an overview of the diagnostic/therapeutic focus of the members of the LASPGHAN and examine the relation of case frequency to year, during the study period. Materials and methods: Latin American pediatric gastroenterologists participated in an online survey, conducted through the SurveyMonkey platform, that investigated the yearly frequency of new inflammatory bowel disease patients within the time frame of 2005–2016, their disease variety, the gastrointestinal segments affected, and the diagnostic and treatment methods utilized. The correlation of new case frequency with each study year was evaluated. Results: A total of 607 patients were studied. The diagnoses were ulcerative colitis in 475 (78.3%) cases, Crohn’s disease in 104 (17.1%), and inflammatory bowel disease D unclassified in 28 (4.6%). The trend in ulcerative colitis was a lineal increase in the frequency of new cases related to each study year, with a significant correlation coefficient. Pancolitis was found in 67.6% of the patients. The diagnostic methods included clinical data, endoscopy, and biopsies in more than 99% of the cases, and imaging studies were indicated selectively. Drug regimens were limited to 5-aminosalicylic acid derivatives, azathioprine, 6-mercaptopurine, infliximab, and adalimumab. Conclusions: Pediatric inflammatory bowel disease in Latin America appears to have increased during the years included in the study period, with a predominance of moderate or severe ulcerative colitis. That lineal trend suggests the predictive likelihood of a gradual increase in the coming years, with possible epidemiologic and clinical implications. Resumen: Introducción y objetivos: El objetivo primario fue explorar la tendencia epidemiológica de la enfermedad intestinal inflamatoria pediátrica en América Latina; los secundarios, obtener una visión general del enfoque diagnóstico/terapéutico de miembros de la SLAGHNP y explorar la relación entre la frecuencia de casos y los años del período evaluado. Material y métodos: Se realizó una encuesta en línea a pediatras gastroenterólogos de América Latina con la plataforma SurveyMonkey. Se preguntó la frecuencia anual de pacientes nuevos de 2005 a 2016, su variedad, los segmentos del tubo digestivo afectados, los métodos de diagnóstico y el tratamiento utilizado. Se evaluó la correlación entre la frecuencia anual y los años de estudio. Resultados: Se estudió a 607 pacientes; el diagnóstico de colitis ulcerativa se realizó en 475 (78.3%), de enfermedad de Crohn en 104 (17.1%) y de enfermedad intestinal inflamatoria no clasificable en 28 (4.6%). La tendencia de colitis ulcerativa tuvo un incremento lineal con coeficiente de correlación significativo entre la frecuencia de casos nuevos y el año de estudio; 67.6% tuvieron pancolitis. Los métodos de diagnóstico incluyeron datos clínicos, endoscopia y biopsias en más del 99% de los casos; los estudios de imagen se indicaron de manera selectiva. Los esquemas farmacológicos se circunscribieron a derivados del ácido 5-aminosalicílico, azatioprina, 6-mercaptopurina, infliximab y adalimumab. Conclusiones: La enfermedad intestinal inflamatoria pediátrica en América Latina parece incrementarse en el período estudiado con predominio de formas moderadas o graves de colitis ulcerativa; esta tendencia lineal puede indicar la posibilidad predictiva de incremento gradual en la próxima década, lo que es probable que tenga implicaciones epidemiológicas y clínicas.

The worldwide prevalence of asymptomatic coeliac disease (CD) is increasing, which is in part due to the routine screening of children with risk factors. Both symptomatic and asymptomatic patients with CD are at risk of long-term complications. The objective of this study was to compare the clinical characteristics of asymptomatic and symptomatic children at the time of CD diagnosis. A case–control study was conducted using data from a cohort of 4838 CD patients recruited from 73 centers across Spain between 2011 and 2017. A total of 468 asymptomatic patients (cases) were selected and matched by age and sex with 468 symptomatic patients (controls). Clinical data, including any reported symptoms, as well as serologic, genetic, and histopathologic data were collected. No significant differences were found between the two groups in most clinical variables, nor in the degree of intestinal lesion. However, the asymptomatic patients were taller (height z-score −0.12 (1.06) vs. −0.45 (1.19), p < 0.001) and were less likely to have anti transglutaminase IgA antibodies ≥ 10 times the upper normal limit (66.2% vs. 758.4%, p = 0.002). Among the 37.1% of asymptomatic patients who were not screened for CD due to the absence of risk factors, only 34% were truly asymptomatic, while the remaining 66% reported non-specific CD-related symptoms. Therefore, expanding CD screening to any child who undergoes a blood test could reduce the burden of care for some children, as many of those considered asymptomatic reported non-specific CD-related symptoms.

Objective: During the SARS-CoV-2 state of alarm (SoA), a 30–70% reduction was observed in the number of visits to Pediatric Emergency Departments (ED), as well as frequent delay in diagnosis or difficulty accessing healthcare services. Here we evaluate modifications observed in pediatric healthcare activity during the SoA. Study design: Descriptive retrospective observational study of the hospital pediatric activity. Method: We compared the use of pediatric healthcare services during the SoA (March 11th – June 25th, 2020) versus the use during the equivalent periods of years 2018 and 2019, in the “Complejo Hospitalario Universitario Insular Materno Infantil de Canarias” (Mother and Child University Hospital of the Canary Islands). Results: The number of patients visiting the pediatric ED decreased by 66.75% on average (95%CI: -65.6; - 67.7; p

One of the most critical moments for young people with intellectual disabilities is their transition to adulthood and employment. It is necessary to make visible the talent of young people with intellectual disabilities to increase the level of employment in this group. Supported employment is a model of inclusion in competitive employment for people with special difficulties. In our work: (1) we analyse the educational system in Wales and the Canary Islands, from the perspective of students with special educational needs; (2) we address the process of transition to employment in both regions, highlighting the main milestones and obstacles to overcome; and (3) we analyse the current situation regarding Supported Employment programmes in Wales and the Canary Islands, highlighting their good practices, such as the Engage to Change Project and the Sinpromi Programme (both programmes promote Supported Employment and are presented as examples of good practice). Although Wales has a more developed vision than the Canary Islands, regarding the transition of young people with intellectual disabilities to employment, there are certain barriers that equally hinder the transition to employment in the two regions. Support, as an element to ensure equal opportunities and to promote the development of a more inclusive and sustainable society, is discussed.

Inborn errors of metabolism (IEM) constitute a huge group of rare diseases affecting 1 in every 1000 newborns. Next-generation sequencing has transformed the diagnosis of IEM, leading to its proposed use as a second-tier technology for confirming cases detected by clinical/biochemical studies or newborn screening. The diagnosis rate is, however, still not 100%. This paper reports the use of a personalized multi-omics (metabolomic, genomic and transcriptomic) pipeline plus functional genomics to aid in the genetic diagnosis of six unsolved cases, with a clinical and/or biochemical diagnosis of galactosemia, mucopolysaccharidosis type I (MPS I), maple syrup urine disease (MSUD), hyperphenylalaninemia (HPA), citrullinemia, or urea cycle deficiency. Eight novel variants in six genes were identified: six (four of them deep intronic) located in GALE, IDUA, PTS, ASS1 and OTC, all affecting the splicing process, and two located in the promoters of IDUA and PTS, thus affecting these genes’ expression. All the new variants were subjected to functional analysis to verify their pathogenic effects. This work underscores how the combination of different omics technologies and functional analysis can solve elusive cases in clinical practice.

Abstract Background The Registry of Adult and Paediatric Patients Treated with Cystadane® – Homocystinuria (RoCH) is a non-interventional, observational, multi-centre, post-authorization safety study that aimed to identify safety of betaine anhydrous (Cystadane®) in the treatment of patients with inborn errors of homocysteine metabolism (homocystinuria) in order to minimise the treatment associated risks and establish better knowledge on its clinical use. The registry included patients of all ages with homocystinuria who were treated with betaine anhydrous in conjunction with other therapies. Clinical data were collected retrospectively from 2007 to 2013, then prospectively up to February 2014. All adverse events (AEs) reported during the study were recorded. The clinical and biological status of patients was monitored at least once a year. Results A total of 125 patients with homocystinuria (adults [> 18 years]: 50; paediatric [≤18 years]: 75) were enrolled at 29 centres in France and Spain. Patients were treated with betaine anhydrous for a mean duration of 7.4 ± 4.3 years. The median total daily dose of betaine anhydrous at the first and last study visits was 6 g/day for cystathionine β-synthase (CBS)-deficient vitamin B6 responders and 9 g/day for methylenetetrahydrofolate reductase-deficient patients, while the median daily dose increased in CBS-deficient B6 non-responders (from 6 to 9 g/day) and cobalamin metabolism-defective patients (from 3 to 6 g/day) between the first and last visits. Treatment caused a mean overall reduction of 29% in plasma homocysteine levels in the study population. A total of 277 AEs were reported during the study, of which two non-serious AEs (bad taste and headache) and one serious AE (interstitial lung disease) were considered to be drug related. Overall, betaine anhydrous was well tolerated with no major safety concerns. Conclusions Data from the RoCH registry provided real-world evidence on the clinical safety and efficacy of betaine anhydrous in the management of homocystinuria in paediatric and adult patients.

Background and Aims: Diagnostic delay (DD) is especially relevant in children with inflammatory bowel disease, leading to potential complications. We examined the intervals and factors for DD in the pediatric population of Spain.Methods: We conducted a multicentric prospective study, including 149 pediatric inflammatory bowel disease patients, obtaining clinical, anthropometric, and biochemical data. Time to diagnosis (TD) was divided into several intervals to identify those where the DD was longer and find the variables that prolonged those intervals. Missed opportunities for diagnosis (MODs) were also identified.Results: Overall TD was 4.4 months (interquartile range [IQR] 2.6–10.4), being significantly higher in Crohn's disease (CD) than in ulcerative colitis (UC) (6.3 [IQR 3.3–12.3] vs. 3 [IQR 1.6–5.6] months, p = 0.0001). Time from the visit to the first physician until referral to a pediatric gastroenterologist was the main contributor to TD (2.4 months [IQR 1.03–7.17] in CD vs. 0.83 months [IQR 0.30–2.50] in UC, p = 0.0001). One hundred and ten patients (78.3%) visited more than one physician (29.9% to 4 or more), and 16.3% visited the same physician more than six times before being assessed by the pediatric gastroenterologist. The number of MODs was significantly higher in CD than that in UC patients: 4 MODs (IQR 2–7) vs. 2 MODs ([IQR 1–5], p = 0.003). Referral by pediatricians from hospital care allowed earlier IBD diagnosis (odds ratio 3.2 [95% confidence interval 1.1–8.9], p = 0.025).Conclusions: TD and DD were significantly higher in CD than those in UC. IBD patients (especially those with CD) undergo a large number of medical visits until the final diagnosis.

The aim of this study was to evaluate for the first time the effect of omega-3 LC PUFA supplementation during pregnancy and lactation on bone metabolism in mothers and neonates. 110 pregnant women were divided in two groups: control group (400 mL/day of the control dairy drink); supplemented group (400 mL/day of the fish oil-enriched dairy drink). Plasma bone biomarkers and mineral content in erythrocyte cytosol were assessed. In mothers, DHA supplementation increased OC and OPN levels and decreased IL-6 and TNF-α levels at delivery, increasing PTH levels during lactation. In neonates, DHA supplementation increased ACTH, insulin and leptin, decreasing RANKL and IL-6 in umbilical vein; increased OPG and leptin and diminished TNF-α in umbilical artery; increased OC levels, lowered PTH and TNF-α at birth. DHA supplementation during pregnancy and lactation has beneficial effects on bone turnover in both mother and neonates, representing a non-pharmacological pathway to decrease bone loss.

Abstract Background Cellular cobalamin defects are a locus and allelic heterogeneous disorder. The gold standard for coming to genetic diagnoses of cobalamin defects has for some time been gene-by-gene Sanger sequencing of individual DNA fragments. Enzymatic and cellular methods are employed before such sequencing to help in the selection of the gene defects to be sought, but this is time-consuming and laborious. Furthermore some cases remain undiagnosed because no biochemical methods have been available to test for cobalamin absorption and transport defects. Results This paper reports the use of massive parallel sequencing of DNA (exome analysis) for the accurate and rapid genetic diagnosis of cobalamin-related defects in a cohort of affected patients. The method was first validated in an initial cohort with different cobalamin defects. Mendelian segregation, the frequency of mutations, and the comprehensive structural and functional analysis of gene variants, identified disease-causing mutations in 12 genes involved in the absorption and synthesis of active cofactors of vitamin B12 (22 cases), and in the non-cobalamin metabolism-related genes ACSF3 (in four biochemically misdiagnosed patients) and SUCLA2 (in one patient with an unusual presentation). We have identified thirteen new variants all classified as pathogenic according to the ACGM recommendation but four were classified as variant likely pathogenic in MUT and SUCLA2. Functional and structural analysis provided evidences to classify them as pathogenic variants. Conclusions The present findings suggest that the technology used is sufficiently sensitive and specific, and the results it provides sufficiently reproducible, to recommend its use as a second-tier test after the biochemical detection of cobalamin disorder markers in the first days of life. However, for accurate diagnoses to be made, biochemical and functional tests that allow comprehensive clinical phenotyping are also needed.

Luis Peña-Quintana,1–3 Marta Llarena,2 Desiderio Reyes-Suárez,2 Luis Aldámiz-Echevarria4 1Pediatric Gastroenterology, Hepatology, and Nutrition Unit, Universitario Materno-Infantil Hospital de Canarias, University of Las Palmas de Gran Canaria, 2Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, Las Palmas, 3CIBEROBN, Madrid, 4Unit of Metabolism, Cruces University Hospital, BioCruces Health Research Institute, GCV-CIBER de Enfremedades Raras (CIBERER), Barakaldo, Spain Abstract: Urea-cycle disorders are a group of rare hereditary metabolic diseases characterized by deficiencies of one of the enzymes and transporters involved in the urea cycle, which is necessary for the removal of nitrogen produced from protein breakdown. These hereditary metabolic diseases are characterized by hyperammonemia and life-threatening hyperammonemic crises. Pharmacological treatment of urea-cycle disorders involves alternative nitrogen-scavenging pathways. Sodium benzoate combines with glycine and phenylacetate/phenylbutyrate with glutamine, forming, respectively, hippuric acid and phenylacetylglutamine, which are eliminated in the urine. Among the ammonia-scavenging drugs, sodium phenylbutyrate is a well-known long-term treatment of urea-cycle disorders. It has been used since 1987 as an investigational new drug, and was approved for marketing in the US in 1996 and the EU in 1999. However, sodium phenylbutyrate has an aversive odor and taste, which may compromise patients’ compliance, and many patients have reported difficulty in taking this drug. Sodium phenylbutyrate granules are a new tasteless and odor-free formulation of sodium phenylbutyrate, which is indicated in the treatment of urea-cycle disorders. This recently developed taste-masked formulation of sodium phenylbutyrate granules was designed to overcome the considerable issues that taste has on adherence to therapy. Several studies have reported the clinical experience of patients with urea-cycle disorders treated with this new tasteless formulation of sodium phenylbutyrate. Analysis of the data indicated that this taste-masked formulation of sodium phenylbutyrate granules improved quality of life for urea-cycle disorder patients. Furthermore, a postmarketing report on the use of the product has confirmed the previous observations of improved compliance, efficacy, and safety with this taste-masked formulation of sodium phenylbutyrate. Keywords: sodium phenylbutyrate granules, urea-cycle disorders, treatment adherence, quality of life

The effect of maternal DHA supplementation on expression of key genes and proteins involved in Fe metabolism and mineral placenta content was evaluated for the first time. One hundred and ten pregnant women were randomly assigned to one of the groups: control (n = 54, 400 ml/day of the control dairy drink; DHA-supplemented (n = 56, 400 ml/day of the DHA-enriched dairy drink). Placenta DMT1, FPN1, TfR1 and Hamp1 mRNA and protein expressions were analysed. Hepcidin concentration in the mother and umbilical cord and placenta mineral content were assessed. DMT1, FPN1, TfR1 and Hamp1 gene expressions together with serum hepcidin increased in umbilical cord and artery of the DHA-supplemented group. In this group, Fe concentration increased in plasma, umbilical cord vein and artery. Ca concentrations raised in umbilical cord vein and artery, Cu, V and Mn levels. Docosahexaenoic acid (DHA) supplementation improved transplacental Fe homeostasis, enhancing Fe transfer and boosting neonates Fe stores at delivery.

Exclusive enteral nutrition (EEN) has been shown to be more effective than corticosteroids in achieving mucosal healing in children with Crohn´s disease (CD) without the adverse effects of these drugs. The aims of this study were to determine the efficacy of EEN in terms of inducing clinical remission in children newly diagnosed with CD, to describe the predictive factors of response to EEN and the need for treatment with biological agents during the first 12 months of the disease. We conducted an observational retrospective multicentre study that included paediatric patients newly diagnosed with CD between 2014–2016 who underwent EEN. Two hundred and twenty-two patients (140 males) from 35 paediatric centres were included, with a mean age at diagnosis of 11.6 ± 2.5 years. The median EEN duration was 8 weeks (IQR 6.6–8.5), and 184 of the patients (83%) achieved clinical remission (weighted paediatric Crohn’s Disease activity index [wPCDAI] < 12.5). Faecal calprotectin (FC) levels (μg/g) decreased significantly after EEN (830 [IQR 500–1800] to 256 [IQR 120–585] p < 0.0001). Patients with wPCDAI ≤ 57.5, FC < 500 μg/g, CRP >15 mg/L and ileal involvement tended to respond better to EEN. EEN administered for 6–8 weeks is effective for inducing clinical remission. Due to the high response rate in our series, EEN should be used as the first-line therapy in luminal paediatric Crohn’s disease regardless of the location of disease and disease activity.

Background Plant-based diets have been linked to high diet quality and reduced risk of cardiovascular diseases. The health impact of plant-based diets might be partially explained by the concomitant intake of flavonoids. Estimation of flavonoids intake in adults has been important for the development of dietary recommendations and interventions for the prevention of weight gain and its consequences. However, estimation of flavonoids intake in children and adolescents is limited. Methods Average daily intake and sources of flavonoids were estimated for a representative national sample of 3,534 children and young people in Spain, aged 2–24 years. The data was collected between 1998 and 2000 by 24-h recalls. The Phenol-Explorer database and the USDA database on flavonoids content were used. Adherence to the Mediterranean diet was measured by the KIDMED index. Results The mean and median intakes of total flavonoids were 70.7 and 48.1 mg/day, respectively. The most abundant flavonoid class was flavan-3-ols (35.7%), with fruit being the top food source of flavonoids intake (42.8%). Total flavonoids intake was positively associated with the KIDMED index (p

La desnutrición en los pacientes hospitalizados tiene repercusiones clínicas y se asocia con peores resultados: inmunodepresión, retraso en la cicatrización de las heridas, atrofia muscular, prolongación del ingreso hospitalario y mayor mortalidad. La tasa de desnutrición al ingreso en el paciente pediátrico varía con los estudios, aunque parece inferior a lo que ocurre en el paciente adulto. Sin embargo, es una población de mayor riesgo de desarrollar desnutrición durante el ingreso. Se precisa, por tanto, encontrar una buena herramienta de cribado nutricional. Objetivo: Como primer paso para alcanzar ese objetivo se realizó un estudio de ámbito nacional para determinar la tasa de desnutrición en el ingreso. Material y métodos: Se trató de un estudio transversal, multicéntrico realizado en 32 hospitales españoles entre junio y septiembre de 2011 en pacientes < 17 años que ingresaran en el hospital por un periodo > 48 horas. Se midieron peso y talla y se pasó el cuestionario STAMP en el momento del ingreso y a los 7, 14 días o en el momento del alta. El estado nutricional se clasificó de acuerdo con el índice de Waterlow para peso y talla. El estudio fue aprobado por el Comité Ético de Investigación de cada uno de los hospitales y se requirió la firma del consentimiento informado antes de su inclusión en el estudio. Resultados: 991 pacientes participaron en el estudio. La edad media fue de 5 años (DE: 4,6), distribuidos de forma uniforme entre todas las edades. Se encontró desnutrición moderada o grave en el 7,8% y sobrepeso-obesidad en el 37,9% de los ingresados. Encontramos una situación nutricional significativamente peor para todos los grupos de edad en función de la enfermedad de base. No encontramos correlación entre la desnutrición y la edad, o los niveles de albúmina sérica. Comentarios: Esta es la primera encuesta nacional para estudiar la prevalencia de desnutrición en el momento del ingreso. La cifra encontrada, 8%, fue ligeramente inferior a la encontrada en otros estudios, probablemente debido a la inclusión de pacientes de hospitales de distinto grado de complejidad, acercándose a lo que sería una muestra real de la población española.

Introducción: Los padres son los principales responsables de la educación nutricional de sus hijos y es labor del pediatra orientar y resolver problemas al respecto. En este estudio se pretende conocer la relevancia de las cuestiones nutricionales en la consulta del pediatra y los principales problemas nutricionales percibidos en los menores de 3 años. Métodos: Estudio descriptivo, transversal en dos fases. La primera consistió en entrevistas y grupos de discusión con 30 pediatras seleccionados aleatoriamente en Madrid y Barcelona. Los resultados se utilizaron para diseñar el cuestionario online (76 preguntas relacionadas con la nutrición en niños de 0-3 años) de la siguiente fase, en la que participaron pediatras seleccionados de forma aleatoria y representativa del territorio nacional. Resultados: De 258 pediatras seleccionados, completaron el cuestionario 151, que atendían a una media de 588 pacientes/mes. Los principales problemas nutricionales percibidos hasta los 12 meses fueron las deficiencias de hierro y vitaminas y la escasa ganancia de peso, y posteriormente la ingesta excesiva de carbohidratos y lípidos y el sobrepeso. Los padres fueron considerados los actores principales en la salud nutricional de sus hijos, pero su preocupación por esta cuestión se reduce significativamente (p < 0,0001) con la edad del niño. Los aspectos considerados más importantes para obtener unos buenos hábitos alimentarios fueron la alimentación adaptada a las necesidades del niño y respetar el tiempo de sueño. El porcentaje de pacientes que recibe recomendaciones de hábitos nutricionales varió del 88% (0-6 meses) al 61% (24-36 meses). Conclusiones: A pesar de considerar la salud nutricional importante, la intervención educativa del pediatra al respecto no es óptima. Los problemas nutricionales percibidos fueron distintos según la edad.Introduction: Parents are most responsible for nutritional education of children, and pediatritians must advise and help them with their doubts. The purpose of this study was to know the relevance of nutritional topics in daily practice and the main nutritional problems perceived by pediatritians in children under 3 years of age. Methods: Descriptive, cross-sectional study performed in 2 stages. First stage consisted on discussion meetings with 30 random-selected pediatritians from Madrid and Barcelona. Results were used to design the on-line questionnaire of the second stage (76 questions related to nutrition in children under 3 years). A random and representative sample of Spanish pediatritians was selected for this stage. Results: One hundred and fifty one pediatritians, among 258 sampled, completed the questionnaire. They referred to see a mean of 588 patients/month. The main perceived nutritional problems in the first year of life were iron and vitamin deficiencies and poor weight gain. In the next months, excess in carbohydrates and lipid intake and overweight were the main problems perceived. Parents were considered the main actors regarding their children's nutritional health, but their concern in these questions significantly reduced with children's age (p < 0,0001). Factors considered to have the greatest relevance in the acquisition of good nutritional habits were to provide a diet adjusted for children's requirements and to observe the appropriate sleeping hours. The proportion of children who receive nutritional counseling varied from 88% (0-6 months) to 61% (24-36 months). Conclusions: Despite of the relevance given by pediatritians, educational intervention regarding nutritional health is not ideal. Nutritional problems perceived by pediatritians varied with children's age.

Este documento presenta un análisis, entre de los intereses de los alumnos y el currículum de la secundaria general. Este estudio se realizó tomando una muestra de cuatro secundarias del municipio de Nuevo Casas Grandes, Chihuahua, a los alumnos se les cuestionó a cerca de sus intereses, para luego hacer la contrastación, con la literatura especializada. Los teóricos al respecto opinan que la educación debe centrarse en el estudiante y sus intereses, pero el currículum de la educación secundaria desde 1974 hasta la fecha, le ha dado relevancia al conocimiento científico (ciencias naturales, ciencias sociales, español y matemáticas), dedicándole la mayor parte del tiempo, espacios e infraestructura, restando importancia a las materias: deportivas, artísticas, tecnológicas y morales. Con esta investigación se pudo comprobar que los intereses de los alumnos están más inclinados hacía, las disciplinas: artísticas, deportivas, tecnológicas y morales. Los alumnos prefieren espacios, tiempos e infraestructura, que les permita convivir más tiempo, en un horario que les permita estar despiertos, para atender con compromiso y pasión, las actividades que desarrollen todas sus capacidades y no preferentemente las capacidades: lógicas, racionales, analíticas, propias del hemisferio cerebral izquierdo. El alumno con su comportamiento: inquieto, distraído, violento, está suplicando, implorando, para que se le deje jugar, imaginar, crear, inventar, innovar.

La infancia es considerada como una etapa trascendental en el proceso evolutivo del hombre, caracterizada por dos fenómenos: crecimiento y desarrollo, para lo cual es fundamental una adecuada nutrición. Los estragos que provoca la desnutrición que se padece en la infancia son los más lamentados por una sociedad, ya que en esta etapa el mayor impacto lo sufre el cerebro del niño, en el que se producirían alteraciones metabólicas y estructurales irreversibles, sin embargo, la desnutrición infantil no es sólo un problema de falta de alimentos, es un conflicto social más profundo, que debe ser tenido en cuenta a la hora de brindar soluciones. La Corporación para la Nutrición Infantil (CONIN), creada en Chile en 1975, tiene por finalidad recuperar a los niños de 0 a 3 años que presentan desnutrición primaria o secundaria. Desde 1993, este proyecto se extendió a la provincia de Mendoza, Argentina, como Fundación CONIN (Cooperadora para la Nutrición Infantil),donde se completó esta experiencia creando Centros de Prevención de Desnutrición. Actualmente este proyecto se desarrolla en distintas provincias del país, en Paraguay y próximamente en Perú, sustentando su trabajo en tres pilares: docencia, asistencia e investigación. CONIN desarrolla una estrategia de intervención de gran impacto sanitario sobre la población de bajos recursos de su área de influencia, con una elevada repercusión social ya que potencia la familia y su entorno como base del correcto desarrollo físico e intelectual del niño, unido a un aporte adecuado de nutrientes, que le permiten al niño desarrollar su potencial genético.Childood is considered a transcendental stage in the evolutionary process of man, characterized by two phenomenon: growth and development, for which a suitable nutrition is fundamental. The damage that causes undernourishment that is suffered in childhood is greatly lamented by society, since in this stage it is the child"s brain that suffers the greatest impact, in which irreversible metabolisms and structural alterarions will occur. Nevertheless, infantundernourishment is not only a problem of lack of fodds, but is also a deeper social conflict, that must be considered at the time of offereing solutions. The Corporation for Childhood Nutrition (CONIN), founded in Chile in 1975, has the mission to help in the recovery of the children from 0 to 3 yearswho present primary or secondary undernourishment.From 1993, this proyect was extended to the province of Mendoza, Argentina, as the CONIN Foundation(Cooperative for Childhood Nutrition), where this experience was completed by creating Undernourishment Prevention Centres. At the moment this project has been developed in different provinces from the country, in Paraguay and in the near future in Peru, sustaining its work on three pillars: teaching, attendance and investigation. CONIN develops a intervention strategy of great impact,in their area of influence, which is used on the low income population. This in turn causes high social repercusions, as the family and its surrounding are reinforced as a basis for the correct physical and intellectual development of the child, together with an adequate nutrients contribution, allowing the child to develop his genetic potential.

El artículo constituye el resultado de una investigación realizada durante septiembre de 2012 a mayo de 2013, con el objetivo de analizar la importancia de la creación del grupo de teatro profesional Alas D’ Cuba, dentro de la creación teatral de la ciudad de Bayamo. A partir de la utilización de entrevista, se obtuvo los criterios de expertos y miembros fundadores del mismo, con la finalidad de definir los rasgos distintivos y evidenciar la calidad y aire renovador que este grupo impregna en la ciudad de Bayamo, Cuba.

Interactions between environmental factors and predisposing genes could be involved in the development of coeliac disease (CD). This study has assessed whether milk-feeding type and HLA-genotype influence the intestinal microbiota composition of infants with a family history of CD. The study included 164 healthy newborns, with at least one first-degree relative with CD, classified according to their HLA-DQ genotype by PCR-SSP DQB1 and DQA1 typing. Faecal microbiota was analysed by quantitative PCR at 7 days, and at 1 and 4 months of age. Significant interactions between milk-feeding type and HLA-DQ genotype on bacterial numbers were not detected by applying a linear mixed-model analysis for repeated measures. In the whole population, breast-feeding promoted colonization of C. leptum group, B. longum and B. breve, while formula-feeding promoted that of Bacteroides fragilis group, C. coccoides-E. rectale group, E. coli and B. lactis. Moreover, increased numbers of B. fragilis group and Staphylococcus spp., and reduced numbers of Bifidobacterium spp. and B. longum were detected in infants with increased genetic risk of developing CD. Analyses within subgroups of either breast-fed or formula-fed infants indicated that in both cases increased risk of CD was associated with lower numbers of B. longum and/or Bifidobacterium spp. In addition, in breast-fed infants the increased genetic risk of developing CD was associated with increased C. leptum group numbers, while in formula-fed infants it was associated with increased Staphylococcus and B. fragilis group numbers. Overall, milk-feeding type in conjunction with HLA-DQ genotype play a role in establishing infants' gut microbiota; moreover, breast-feeding reduced the genotype-related differences in microbiota composition, which could partly explain the protective role attributed to breast milk in this disorder.