Congenital Erythrocytosis (CE), also called congenital polycythemia, represents a rare and heterogeneous clinical entity. It is caused by deregulated red blood cell production where erythrocyte overproduction results in elevated hemoglobin and hematocrit levels. 3Primary congenital familial erythrocytosis is associated with low erythropoietin (Epo) levels and generally results from mutations in the erythropoietin-receptor gene (EPOR).Secondary congenital erythrocytosis arises from conditions which cause tissue hypoxia thus resulting in increased Epo production. These include hemoglobin variants with increased affinity for oxygen (genes HBB, HBA1 and HBA2), decreased production of 2,3-biphosphoglycerate due to mutations in the BPGM gene, or mutations in the genes involved in the hypoxia sensing pathway (VHL, EPAS1 and EGLN1). Depending on the affected gene CE can be inherited either in an autosomal dominant or recessive mode, with sporadic cases arising de novo.Despite recent important discoveries in the molecular pathogenesis of CE, the molecular causes remain to be identified in about 70% of the patients.With the objective of collecting all the published and unpublished cases of CE the COST action MPN&MPNr-Euronet developed a comprehensive internet-based database focusing on the registration of clinical history, hematological, biochemical and molecular data (http://www.erythrocytosis.org/). In addition, unreported mutations are also curated in the corresponding Leiden Open Variation Database (LOVD).

IntroductionCongenital Erythrocytosis can be classified as primary, when the defect is intrinsic to the RBC progenitors and independent of the serum erythropoietin (Epo) concentration, or secondary, when the erythrocytosis is the result of an up-regulation of Epo production. Primary erythrocytosis is associated with mutations in the EPOR gene, secondary congenital erythrocytosis can de due to mutations that stabilize the hemoglobin in the oxygenated form or to mutations in the genes that control the transcriptional activation of the EPO gene -VHL, EGLN1, EPAS1. Material and MethodsWith the main objective of describing the etiology and molecular basis of congenital erythrocytosis we have studied 70 consecutive unrelated patients presenting with idiopathic erythrocytosis from our hematology clinic or referred from other centers. According to a study algorithm we have sequenced all the genes described as associated with congenital erythrocytosis. Results and DiscussionErythrocytosis molecular etiology was identify in 25 (36%) of the 70 subjects. High-affinity Hb variants were the most common cause, present in 20% of the cases. New mutations were identified in the JAK2, EPOR, VHL and EGLN1 genes. Conclusions High affinity hemoglobin variants are a very rare cause of secondary congenital erythrocytosis, but it seems likely that their incidence may be underestimated. Our experience shows that in erythrocytosis with a dominant inheritance and normal or inappropriate high Epo levels, the HBB and HBA genes should be the first to be studied. In spite of the seven genes known to be involved in congenital erythrocytosis, the majority of the cases have unknown etiology.

The diagnosis of von Willebrand disease (VWD), the most common inherited bleeding disorder, is characterised by a variable bleeding tendency and heterogeneous laboratory phenotype. The sequencing of the entire VWF coding region has not yet become a routine practice in diagnostic laboratories owing to its high costs. Nevertheless, next-generation sequencing (NGS) has emerged as an alternative to overcome this limitation. We aimed to determine the correlation of genotype and phenotype in 92 Portuguese individuals from 60 unrelated families with VWD; therefore, we directly sequenced VWF. We compared the classical Sanger sequencing approach and NGS to assess the value-added effect on the analysis of the mutation distribution in different types of VWD. Sixty-two different VWF mutations were identified, 27 of which had not been previously described. NGS detected 26 additional mutations, contributing to a broad overview of the mutant alleles present in each VWD type. Twenty-nine probands (48.3 %) had two or more mutations; in addition, mutations with pleiotropic effects were detected, and NGS allowed an appropriate classification for seven of them. Furthermore, the differential diagnosis between VWD 2B and platelet type VWD (n = 1), Bernard-Soulier syndrome and VWD 2B (n = 1), and mild haemophilia A and VWD 2N (n = 2) was possible. NGS provided an efficient laboratory workflow for analysing VWF. These findings in our cohort of Portuguese patients support the proposal that improving VWD diagnosis strategies will enhance clinical and laboratory approaches, allowing to establish the most appropriate treatment for each patient.

Introduction: The importance of hydration is undoubtable but reliable data on hydration status and its relation with diet is lacking. Objectives: We aimed to evaluate the hydration status and its relation to beverages and food intake in children. Methods: A sample of 172 (50% male), 7-11 year-old children was included in this survey. Participants completed a 24 h urine collection; a 24 hours food recall corresponding to the day of urine collection was applied, weight and height were measured and parents/caregivers fi lled a lifestyle and socio-demographic questionnaire. The free water reserve was used to assess the hydration status. The intakes of food and beverages were compared according to hydration status using the t-test, Mann-Whitney test or unconditional regression models as appropriate. Results: More than half of the participants were classifi ed as hypohydrated or at risk of hypohydration (57% in girls and 58% in boys). Compared to hypohydrated children, a signifi cant higher consumption of water (276.2 ± 208.4 vs 188.2 ± 187.4 g/day) and fruit juices (77.6 ± 139.4 vs 14.4 ± 57.2 g/day) was reported by euhydrated boys and girls, respectively. Lower consumers of water and fruit juices showed a higher risk of hypohydration (OR = 2.16, 95% CI: 1.02-4.58, p = 0.045), adjusting for confounders. Conclusions: Most of the children included in this analysis were classifi ed as at risk of hypohydration and those with higher water and fruit juices consumption showed a better hydration status.

Clinical and demographical risk factors for disabling CD and reoperation were determined and their impact was quantified by means of risk matrices, which are applicable as bedside clinical tools that can help physicians during therapeutic decisions in early disease management.

Although neither early surgery nor immunosuppression seem to be able to prevent global disabling disease, an early start of immunosuppression by itself is associated with fewer surgeries and should be considered in daily practice as a preventive strategy.

BackgroundData from studies assessing the intake of potassium, and the concomitant sodium-to-potassium ratio are limited. The aim of this study was to evaluate potassium and sodium-to-potassium ratio intake in 8–10 year-old children.MethodsA cross-sectional survey was carried out from January to June 2014 and data from 163 children (81 boys) were included. Potassium intake was estimated by 24-h urine collection and coefficient of creatinine was used to validate completeness of urine collections. Urinary sodium and sodium-to-potassium ratio were also analysed. A 24-h dietary recall was used to provide information on dietary sources of potassium. Height and weight were measured according to international standards.ResultsThe mean urinary potassium excretion was 1701 ± 594 mg/day in boys, and 1682 ± 541 mg/day in girls (p = 0.835); 8.0 % of children met the WHO recommendations for potassium intake. The mean sodium excretion was 2935 ± 1075 mg/day in boys and 2381 ± 1045 mg/day in girls (p <0.001) and urinary sodium-to-potassium ratio was 3.2 ± 1.4 in boys, and 2.5 ± 1.1 in girls (p = 0.002). The mean fruit and vegetable intake was 353.1 ± 232.5 g/day in boys, and 290.8 ± 213.1 g/day in girls (p = 0.101).ConclusionsThis study reported a low compliance of potassium intake recommendations in 8–10 year-old children. Health promotion interventions are needed in order to broaden public awareness of potassium inadequacy and to increase potassium intake.

Biodegradable polydioxanone stents were developed for the treatment of refractory benign esophageal strictures but have been suggested as a new therapeutic option for intestinal strictures. The primary advantage of biodegradable stents over self-expandable metallic stents is that removal is not required. There are, however, few data available on their use in the small or large bowel. We herein describe the case of a 33-year-old patient with long-standing Crohn's disease (CD) who developed a fibrotic stricture of the sigmoid too long to be amenable to balloon dilation. The use of a biodegradable polydioxanone stent was chosen to avoid surgery. Combined endoscopic and fluoroscopic placement of the stent was technically simple, safe and clinically successful, and no recurrence of obstructive symptoms occurred during a 16-mo follow-up. Further studies are needed to evaluate the long-term efficacy and safety of biodegradable stents in the treatment of intestinal strictures, particularly in the context of CD.