Vitamin D is essential for the normal mineralization of bones during childhood. Although diet and adequate sun exposure should provide enough of this nutrient, there is a high prevalence of vitamin D ...deficiency rickets worldwide. Children with certain conditions that lead to decreased vitamin D production and/or absorption are at the greatest risk of nutritional rickets. In addition, several rare genetic alterations are also associated with severe forms of vitamin-D-resistant or -dependent rickets. Although vitamin D3 is the threshold nutrient for the vitamin D endocrine system (VDES), direct measurement of circulating vitamin D3 itself is not a good marker of the nutritional status of the system. Calcifediol (or 25(OH)D) serum levels are used to assess VDES status. While there is no clear consensus among the different scientific associations on calcifediol status, many clinical trials have demonstrated the benefit of ensuring normal 25(OH)D serum levels and calcium intake for the prevention or treatment of nutritional rickets in childhood. Therefore, during the first year of life, infants should receive vitamin D treatment with at least 400 IU/day. In addition, a diet should ensure a normal calcium intake. Healthy lifestyle habits to prevent vitamin D deficiency should be encouraged during childhood. In children who develop clinical signs of rickets, adequate treatment with vitamin D and calcium should be guaranteed. Children with additional risk factors for 25(OH)D deficiency and nutritional rickets should be assessed periodically and treated promptly to prevent further bone damage.
Abstract
We tested the idea that functional trade‐offs that underlie species tolerance to drought drive shifts in community composition via their effects on demographic processes and subsequently on ...shifts in species' abundance. Using data from 298 tree species from tropical dry forests during the extreme ENSO‐2015, we scaled‐up the effects of trait trade‐offs from individuals to communities. Conservative wood and leaf traits favoured slow tree growth, increased tree survival and positively impacted species abundance and dominance at the community‐level. Safe hydraulic traits, on the other hand, were related to demography but did not affect species abundance and communities. The persistent effects of the conservative–acquisitive trade‐off across organizational levels is promising for generalization and predictability of tree communities. However, the safety–efficient trade‐off showed more intricate effects on performance. Our results demonstrated the complex pathways in which traits scale up to communities, highlighting the importance of considering a wide range of traits and performance processes.
Type III Bartter syndrome (BS) is an autosomal recessive renal tubule disorder caused by loss-of-function mutations in the CLCNKB gene, which encodes the chloride channel protein ClC-Kb. In this ...study, we carried out a complete clinical and genetic characterization in a cohort of 30 patients, one of the largest series described. By comparing with other published populations, and considering that 80% of our patients presented the p.Ala204Thr Spanish founder mutation presumably associated with a common phenotype, we aimed to test the hypothesis that allelic differences could explain the wide phenotypic variability observed in patients with type III BS.
Clinical data were retrieved from the referral centers. The exon regions and flanking intronic sequences of the CLCNKB gene were screened for mutations by polymerase chain reaction (PCR) followed by direct Sanger sequencing. Presence of gross deletions or duplications in the region was checked for by MLPA and QMPSF analyses.
Polyuria, polydipsia and dehydration were the main common symptoms. Metabolic alkalosis and hypokalemia of renal origin were detected in all patients at diagnosis. Calciuria levels were variable: hypercalciuria was detected in 31% of patients, while 23% had hypocalciuria. Nephrocalcinosis was diagnosed in 20% of the cohort. Two novel CLCNKB mutations were identified: a small homozygous deletion (c.753delG) in one patient and a small deletion (c.1026delC) in another. The latter was present in compound heterozygosis with the already previously described p.Glu442Gly mutation. No phenotypic association was obtained regarding the genotype.
A poor correlation was found between a specific type of mutation in the CLCNKB gene and type III BS phenotype. Importantly, two CLCNKB mutations not previously described were found in our cohort.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Monogenic diabetes can be misdiagnosed as type 1 or type 2 diabetes in children. The right diagnosis is crucial for both therapeutic choice and prognosis and influences genetic counseling. The main ...objective of this study was to search for monogenic diabetes in Spanish pediatric patients suspected of type 1 diabetes with lack of autoimmunity at the onset of the disease. We also evaluated the extra value of ZnT8A in addition to the classical IAA, GADA and IA2A autoantibodies to improve the accuracy of type 1 diabetes diagnosis.
Four hundred Spanish pediatric patients with recent-onset diabetes (mean age 8.9 ± 3.9 years) were analyzed for IAA, GADA, IA2A and ZnT8A pancreatic-autoantibodies and HLA-DRB1 alleles. Patients without autoimmunity and those with only ZnT8A positive were screened for 12 monogenic diabetes genes by next generation sequencing.
ZnT8A testing increased the number of autoantibody-positive patients from 373 (93.3%) to 377 (94.3%). An isolated positivity for ZnT8A allowed diagnosing autoimmune diabetes in 14.8% (4/27) of pediatric patients negative for the rest of the antibodies tested. At least 2 of the 23 patients with no detectable autoimmunity (8%) carried heterozygous pathogenic variants: one previously reported missense variant in the INS gene (p.Gly32Ser) and one novel frameshift variant (p.Val264fs) in the HNF1A gene. One variant of uncertain significance was also found. Carriers of pathogenic variants had HLA-DRB1 risk alleles for autoimmune diabetes and clinical characteristics compatible with type 1 diabetes except for the absence of autoimmunity.
ZnT8A determination improves the diagnosis of autoimmune diabetes in pediatrics. At least 8% of pediatric patients suspected of type 1 diabetes and with undetectable autoimmunity have monogenic diabetes and can benefit from the correct diagnosis of the disease by genetic study.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tropical dry forests (TDF) are known to be resource‐limited due to a marked seasonality in precipitation. However, TDF are also shaped by factors such as solar radiation, wind speed, soil fertility, ...and land‐cover transformation. Together, these factors may determine different gradients of environmental harshness that are likely to drive changes in plant community attributes. Here, we evaluated the effects of environmental harshness on plant community diversity and structure of Colombian TDF, based on floristic and environmental data from 15 1‐ha permanent plots. We also analyzed these effects on legumes species only (including both deciduous and non‐deciduous species), deciduous species only (including both legumes and non‐legumes species), and on the whole community excluding either legumes or deciduous separately. Drier conditions and higher land‐cover transformation had the strongest negative effects on species diversity, basal area (BA), and canopy height. Soil fertility, on the contrary, did not have a significant effect on any of the evaluated response variables. Interestingly, legumes maintained their diversity and BA along the climatic gradient, while deciduous species were negatively affected by drier conditions and by an increase in secondary vegetation at the landscape level. Our results suggest that although TDF are limited by water availability, land‐cover transformation strongly increases environmental harshness. Yet, both legumes and deciduous species were differentially impacted by climatic and land transformation variables. Thus, to better understand TDF plant community attributes, it is necessary to consider these gradients and to disentangle their effects on different plant functional groups.
in Spanish is available with online material.
Resumen
Es ampliamente conocido que los bosques secos tropicales (BST) tienen fuertes limitaciones de recursos derivadas de estacionalidad de la precipitación. Sin embargo, otros factores como la radiación solar, la velocidad del viento, la fertilidad de los suelos y la transformación de las coberturas también dan forma a las condiciones ambientales restrictivas de este ecosistema. En conjunto, estos factores determinan la dureza ambiental que rige el BST y probablemente explican los cambios en los atributos comunitarios de las plantas a lo largo de gradientes. Evaluamos los efectos de la dureza ambiental sobre la diversidad de plantas y atributos estructurales del BST con base en datos florísticos y ambientales para 15 parcelas permanentes de 1 ha, para toda la comunidad de plantas, y subgrupos de plantas que incluyeron solo especies de leguminas y solo caducifolias por separado. Las condiciones secas y coberturas altamente transformadas tuvieron los efectos negativos sobre la diversidad de especies, el área basal y la altura del dosel a nivel comunitario, mientras que la fertilidad del suelo no afectó a ninguno de los atributos evaluados. Interesantemente, el grupo de especies leguminosas mantuvieron su diversidad y área basal a lo largo del gradiente de severidad climática, mientras que el grupo de especies de hoja caduca se vio negativamente afectado por las condiciones más secas y el aumento en el área de coberturas secundarias. Nuestros resultados sugieren que, aunque el BST esta claramente limitado por la disponibilidad del agua, la transformación de las coberturas naturales impulsa el aumento de la dureza ambiental en este ecosistema. Donde, las especies de leguminosas y caducifolias se ven afectadas de manera diferente a toda la comunidad de plantas. De tal forma, para un mejor entendimiento de como cambian los atributos comunitarios de las plantas en los BST es necesario tener en cuenta todas las fuentes de variación ambiental, así como, desagregar los efectos particulares para determinados grupos funcionales de plantas.
Background
Primary distal renal tubular acidosis (dRTA) is a rare genetic disorder caused by impaired distal mechanisms of urinary acidification. Most cases are secondary to pathogenic variants in
...ATP6V0A4
,
ATP6V1B1
, and
SLC4A1
genes, which encode transporters regulating acid-base balance in the collecting duct.
Methods
Retrospective study of molecular and clinical data from diagnosis and long-term follow-up (10, 20, and 40±10 years) of 16 patients with primary dRTA diagnosed in childhood.
Results
Molecular analyses revealed nine patients had
ATP6V0A4
pathogenic variants, five in
ATP6V1B1
, and two in
SLC4A1
. A novel intragenic deletion and a common
ATP6V0A4
gene variant (c.1691 + 2dupT) in
ATP6V0A4
occurred in two-thirds of these patients, suggesting a founder effect. Median age at diagnosis was 3.25 months (IQR 1, 13.5), which was higher in the
SLC4A1
group. Median SDS height at diagnosis was −1.02 (IQR −1.79, 0.14). Delayed clinical diagnosis was significantly related to growth failure (
P
= 0.01). Median SDS height at 20 years follow-up was −1.23 (IQR −1.71, −0.48), and did not significantly improve from diagnosis (P = 0.76). Kidney function declined over time: at last follow-up, 43% had moderate to severe chronic kidney disease (CKD). Adequate metabolic control was not related to CKD development. Incidence of sensorineural hearing loss (SNHL) was high in
ATP6V1B1
patients, though not universal. Patients harboring
ATP6V0A4
variants also developed SNHL at a high rate (80%) over time.
Conclusions
Patients with dRTA can develop moderate to severe CKD over time with a high frequency despite adequate metabolic control. Early diagnosis ameliorates long-term height prognosis.
Tropical dry forests (TDFs) have been defined as a single biome occurring mostly in the lowlands where there is a marked period of drought during the year. In the Neotropics, dry forests occur across ...contrasting biogeographical regions that contain high beta diversity and endemism, but also strong anthropogenic pressures that threaten their biodiversity and ecological integrity. In Colombia, TDFs occur across six regions with contrasting soils, climate, and anthropogenic pressures, therefore being ideal for studying how these variables relate to dry forest species composition, successional stage and conservation status. Here, we explore the variation in climate and soil conditions, floristic composition, forest fragment size and shape, successional stage and anthropogenic pressures in 571 dry forest fragments across Colombia. We found that TDFs should not be classified solely on rainfall seasonality, as high variation in precipitation and temperature were correlated with soil characteristics. In fact, based on environmental factors and floristic composition, the dry forests of Colombia are clustered in three distinctive groups, with high species turnover across and within regions, as reported for other TDF regions of the Neotropics. Widely distributed TDF species were found to be generalists favored by forest disturbance and the early successional stages of dry forests. On the other hand, TDF fragments were not only small in size, but highly irregular in shape in all regions, and comprising mostly early and intermediate successional stages, with very little mature forest left at the national level. At all sites, we detected at least seven anthropogenic disturbances with agriculture, cattle ranching and human infrastructure being the most pressing disturbances throughout the country. Thus, although environmental factors and floristic composition of dry forests vary across regions at the national level, dry forests are equally threatened by deforestation, degradation and anthropogenic pressures all over the country, making TDFs a top priority for conservation in Colombia.
The disorders in the metabolism of calcium can present with manifestations that strongly suggest their diagnosis; however, most of the time, the symptoms with which they are expressed are nonspecific ...or present only as a laboratory finding, usually hypercalcemia. Because many of these disorders have a genetic etiology, in the present study, we sequenced a selection of 55 genes encoding the principal proteins involved in the regulation of calcium metabolism.
A cohort of 79 patients with hypercalcemia were analyzed by next-generation sequencing.
The 30% of our cohort presented one pathogenic or likely pathogenic variant in genes associated with hypercalcemia. We confirmed the clinical diagnosis of 17 patients with hypocalciuric hypercalcemia (pathogenic or likely pathogenic variants in the
and
genes), one patient with neonatal hyperparathyroidism (homozygous pathogenic variant in the
gene), and another patient with infantile hypercalcemia (two pathogenic variants in compound heterozygous state in the
gene). However, we also found variants in genes associated with primary hyperparathyroidism (
), renal hypophosphatemia with or without rickets (
,
,
,
, and
), DiGeorge syndrome (
and
), and hypophosphatasia (
). Our genetic study revealed 11 novel variants.
Our study demonstrates the importance of genetic analysis through massive sequencing to obtain a clinical diagnosis of certainty. The identification of patients with a genetic cause is important for the appropriate treatment and identification of family members at risk of the disease.
The aim of this study was to estimate the incidence of diabetes mellitus in the Basque Country and the risk factors involved in the disease by reassessing an adult population after 7 years of ...follow-up. In the previous prevalence study, 847 people older than 18 years were randomly selected from all over the Basque Country and were invited to answer a medical questionnaire, followed by a physical examination and an oral glucose tolerance test. In the reassessment, the same variables were collected and the resulting cohort comprised 517 individuals of whom 43 had diabetes at baseline. The cumulative incidence of diabetes was 4.64% in 7 years and the raw incidence rate was 6.56 cases/1000 person-years (95%CI: 4.11-9.93). Among the incident cases, 59% were undiagnosed. The most strongly associated markers by univariate analyses were age > 60 years, dyslipidaemia, prediabetes and insulin resistance. We also found association with hypertension, obesity, family history of diabetes and low education level. Multivariate analysis adjusted for age and sex showed that a set of risk factors assessed together (dyslipidaemia, waist-to-hip-ratio and family history of diabetes) had great predictive value (AUC-ROC = 0.899, 95%CI: 0.846-0.953, p = 0.942), which suggests the need for early intervention before the onset of prediabetes.
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