Atypical hematological manifestation of celiac disease: A case report of aplastic anemia in a 2-year-old child and review of the literature.

INTRODUCTION: Celiac disease typically presents with symptoms of malabsorption, but extraintestinal manifestations are increasingly reported. Aplastic anemia as the mode of celiac disease presentation is extremely rare in children. CASE PRESENTATION: We report a 2-year-old boy who presented with loose stools, loss of appetite, and bicytopenia with severe aregenerative normocytic anemia. Investigations, including bone marrow aspirate and biopsy, revealed aplastic anemia. Screening for malabsorption showed increased plasma concentrations of anti-transglutaminase and anti-gliadin antibodies. A duodenal biopsy confirmed the histologic features of celiac disease. The child received a packed red cell transfusion and was started on a gluten-free diet, with a very good prognosis and normalization of both his blood and histological parameters. To the best of our knowledge, our report is the sixth pediatric case in the literature. CONCLUSION: Screening for celiac disease should be performed in children with unexplained hematological abnormalities such as aplastic anemia with or without gastrointestinal symptoms.

Spot urine samples to estimate 24-hour urinary calcium excretion in school-age children.

Urinary calcium/creatinine ratio (UCa/Cr) on a single spot urine sample is frequently used in children to evaluate calciuria, but its accuracy to estimate 24-h urinary calcium excretion (24hUCa) has not been properly assessed. We analyzed the correlation between UCa/Cr in various spot samples and 24hUCa among healthy children. A 24-h urine specimen and three spot urine samples (evening, first, and second morning) were collected in a convenience sample of children aged 6 to 16 years (n = 101). Measured 24hUCa was compared with UCa/Cr in each of the three spot samples. The ability of UCa/Cr to discriminate between children with and without hypercalciuria (calciuria > 4 mg/kg/24 h, 1 mmol/kg/24 h) and optimal timing of the spot sample were determined. Eighty-five children completed an adequate 24-h urine collection. Pearson correlation coefficients between the UCa/Cr on the spot sample and 24hUCa were 0.64, 0.71, and 0.52 for the evening, first, and second morning spot samples, respectively. Areas under the ROC curve were 0.90, 0.82, and 0.75, respectively, for the corresponding spot samples.Conclusion: The relatively strong correlation between 24hUCa and UCa/Cr in evening and first morning spot urine samples suggests that these spots could be preferred in clinical practice.Trial registration: ClinicalTrials.gov , NCT02900261, date of trial registration 14 September 2016. What is Known: •Urinary calcium/creatinine ratio on a single spot urine sample is frequently used as a proxy for 24-h urinary calcium excretion. •Correlation of these indicators, including the best timing for spot urine sampling, has not been properly assessed. What is New: •Relatively strong correlations were found between the calcium/creatinine ratio on a single spot urine sample and 24-h urinary calcium excretion in healthy children. •Evening and first morning spot samples had the highest correlation.

Monitoring caffeine intake in children with a questionnaire and urine collection: a cross-sectional study in a convenience sample in Switzerland.

PURPOSE: The objectives of this study were (1) to estimate caffeine intake and identify the main sources of intake using a dietary questionnaire, (2) to assess 24-h urinary excretion of caffeine and its metabolites, and (3) to assess how self-reported intake estimates correlates with urinary excretion among children in Switzerland. METHODS: We conducted a cross-sectional study of children between 6 and 16 years of age in one region of Switzerland. The participants filled in a dietary questionnaire and collected a 24-h urine sample. Caffeine intake was estimated with the questionnaire. Caffeine, paraxanthine, theophylline, and theobromine excretions were measured in the urine sample. Correlations between questionnaire-based intake and urinary excretion estimates were assessed using Spearman correlation coefficients. RESULTS: Ninety-one children were included in the analysis (mean age 10.6 years; 43% female). The mean daily caffeine intake estimate derived from the diet questionnaire was 39 mg (range 0-237), corresponding, when related to body weight, to 1.2 mg/kg (range 0.0-6.3). Seven children (8%) had a caffeine intake above the upper recommended level of 3 mg/kg per day. The main sources of caffeine intake were cocoa milk (29%), chocolate (25%), soft drinks (11%), mocha yogurt (10%), tea (8%), and energy drinks (8%). The 24-h urinary excretion of caffeine was 0.3 mg (range 0.0-1.5), paraxanthine 1.4 mg (range 0.0-7.1), theophylline 0.1 mg (range 0.0-0.6), and theobromine 14.8 mg (range 0.3-59.9). The correlations between estimates of caffeine intake and the 24-h urinary excretion of caffeine was modest (ρ = 0.21, p = 0.046) and with the metabolites of caffeine were weak (ρ = 0.09-0.11, p = 0.288-0.423). CONCLUSIONS: Caffeine intake in a sample of children in a region of Switzerland was relatively low. The major sources of intake were cocoa milk, chocolate and soft drinks. Self-reported caffeine intake correlated weakly with urinary excretion of caffeine and some of its main metabolites. TRIAL REGISTRATION NUMBER: NCT02900261.

Nebulised hypertonic saline in moderate-to-severe bronchiolitis: a randomised clinical trial.

OBJECTIVES: To investigate whether nebulised hypertonic saline (HS) treatment would decrease length of hospital stay (LOS) among infants with moderate-to severe-bronchiolitis compared with standard supportive care (SC). METHODS: We conducted an open, multicentre, randomised clinical trial from 1 April 2013 to 31 March 2016, in Swiss children's hospitals. Patients aged 6 weeks to 24 months with a primary diagnosis of moderate or severe bronchiolitis were included. Children with previous episodes of wheezing, cardiac disease, chronic respiratory disease, immunodeficiency, prematurity (gestational age <34 weeks), corticotherapy in the preceding 2 weeks or inhaled bronchodilators within 24 hours before presentation were excluded. Patients were randomised to receive standard SC with nebulisation of 4 mL of 3% sodium chloride every 6 hours versus SSC. Main outcomes and measures were LOS duration of oxygen therapy, transfer to intensive care unit (ICU), readmission within 7 days following discharge and adverse events. RESULTS: 121 children were randomised. No statistically significant differences were found between treatment groups at baseline (age, Wang Score, atopic history, smoking exposure). Children in the HS group had a non-significant difference in length of stay -2.8 hours (-10; 16) compared with the SC group. There were no differences in oxygen therapy duration, transfer to ICU, readmission rate or adverse events. The intervention was discontinued at the parents' request in 16% of the cases. CONCLUSION: Our study does not support the use of HS nebulisation in children with moderate to severe bronchiolitis. TRIAL REGISTRATION NUMBER: NCT01812525.

Estimation of salt intake and excretion in children in one region of Switzerland: a cross-sectional study.

PURPOSE: Salt intake among children in Switzerland is unknown. The objectives of this study were to determine salt excretion and to identify the main dietary sources of salt intake among children in one region of Switzerland. METHODS: We conducted a cross-sectional study using a convenient sample of children 6-16 years of age in Valais, Switzerland, between 2016 and 2018. All children visiting several regional health care providers and without any clinical condition that could affect sodium intake or excretion were eligible. Each child completed a 24-h urine collection to assess salt excretion and two dietary questionnaires to assess dietary sources of salt intake. Weight and height were measured. RESULTS: Data were available on 94 children (55 boys and 39 girls; mean age 10.5 years; age range 6-16 years). The mean 24-h salt urinary excretion was 5.9 g [SD 2.8; range 0.8-16.0; 95% confidence interval (CI) 5.3-6.5]. Two-thirds (62%) of the children had salt excretions above recommendations of maximum intake (i.e., ≥ 2 g per day for children up to 6 years of age and ≥ 5 g per day for children 7-16 years of age). The salt excretion tended to be higher during the week-end (6.0 g, 95% CI 5.4-6.6) than during the week (5.4 g, 95% CI 4.3-6.7). The main sources of salt intake were pastas, potatoes, and rice (23% of total salt intake), pastries (16%), bread (16%), and cured meats (10%). One child out of three (34%) added salt to their plate at the table. CONCLUSIONS: Salt intake in children in one region of Switzerland was high. Our findings suggest that salt intake in children could be reduced by lowering salt content in commonly eaten foods. TRIAL REGISTRATION NUMBER: NCT02900261.

Urine Spot Samples Can Be Used to Estimate 24-Hour Urinary Sodium Excretion in Children.

Background: The gold standard to assess salt intake is 24-h urine collections. Use of a urine spot sample can be a simpler alternative, especially when the goal is to assess sodium intake at the population level. Several equations to estimate 24-h urinary sodium excretion from urine spot samples have been tested in adults, but not in children. Objective: The objective of this study was to assess the ability of several equations and urine spot samples to estimate 24-h urinary sodium excretion in children. Methods: A cross-sectional study of children between 6 and 16 y of age was conducted. Each child collected one 24-h urine sample and 3 timed urine spot samples, i.e., evening (last void before going to bed), overnight (first void in the morning), and morning (second void in the morning). Eight equations (i.e., Kawasaki, Tanaka, Remer, Mage, Brown with and without potassium, Toft, and Meng) were used to estimate 24-h urinary sodium excretion. The estimates from the different spot samples and equations were compared with the measured excretion through the use of several statistics. Results: Among the 101 children recruited, 86 had a complete 24-h urine collection and were included in the analysis (mean age: 10.5 y). The mean measured 24-h urinary sodium excretion was 2.5 g (range: 0.8-6.4 g). The different spot samples and equations provided highly heterogeneous estimates of the 24-h urinary sodium excretion. The overnight spot samples with the Tanaka and Brown equations provided the most accurate estimates (mean bias: -0.20 to -0.12 g; correlation: 0.48-0.53; precision: 69.7-76.5%; sensitivity: 76.9-81.6%; specificity: 66.7%; and misclassification: 23.0-27.7%). The other equations, irrespective of the timing of the spot, provided less accurate estimates. Conclusions: Urine spot samples, with selected equations, might provide accurate estimates of the 24-h sodium excretion in children at a population level. At an individual level, they could be used to identify children with high sodium excretion. This study was registered at clinicaltrials.gov as NCT02900261.

NBAS mutations cause a multisystem disorder involving bone, connective tissue, liver, immune system, and retina.

We report two unrelated patients with a multisystem disease involving liver, eye, immune system, connective tissue, and bone, caused by biallelic mutations in the neuroblastoma amplified sequence (NBAS) gene. Both presented as infants with recurrent episodes triggered by fever with vomiting, dehydration, and elevated transaminases. They had frequent infections, hypogammaglobulinemia, reduced natural killer cells, and the Pelger-Huët anomaly of their granulocytes. Their facial features were similar with a pointed chin and proptosis; loose skin and reduced subcutaneous fat gave them a progeroid appearance. Skeletal features included short stature, slender bones, epiphyseal dysplasia with multiple phalangeal pseudo-epiphyses, and small C1-C2 vertebrae causing cervical instability and myelopathy. Retinal dystrophy and optic atrophy were present in one patient. NBAS is a component of the synthaxin-18 complex and is involved in nonsense-mediated mRNA decay control. Putative loss-of-function mutations in NBAS are already known to cause disease in humans. A specific founder mutation has been associated with short stature, optic nerve atrophy and Pelger-Huët anomaly of granulocytes (SOPH) in the Siberian Yakut population. A more recent report associates NBAS mutations with recurrent acute liver failure in infancy in a group of patients of European descent. Our observations indicate that the phenotypic spectrum of NBAS deficiency is wider than previously known and includes skeletal, hepatic, metabolic, and immunologic aspects. Early recognition of the skeletal phenotype is important for preventive management of cervical instability.