Hypovitaminosis D in Healthy Pregnant Women and their Newborns in Greece.

BACKGROUND/OBJECTIVES: The aim of this work was to evaluate the current vitamin D status in healthy pregnant women and their newborns living in Greece and assess possible associations between 25(OH)D and anthropometric features of their fetuses and newborns. MATERIALS & METHODS: 81 healthy women were monitored during pregnancy. Biochemical markers related to bone metabolism, 25(OH)D and PTH levels were measured in serum samples of mothernewborn pairs at 1st trimester of pregnancy and at delivery in mothers, in cord blood and at the 3rd day of life of newborns. RESULTS: Maternal 25(OH)D levels at the 1st trimester of pregnancy (22.6±9.2ng/ml) were significantly higher than those at delivery (19.2±9.2ng/ml) (p<0.001). Furthermore, umbilical 25(OH)D levels (21.3±9.3ng/ml) were higher than maternal at delivery (p=0.005) and neonatal levels (19.4±10.4 ng/ml) (p=0.021). Only 57.3% of the mothers at the first trimester and 46.7% at delivery as well as 55.8% of the fetuses and 38.5% of the neonates had adequate vitamin D levels (25(OH)D≥30ng/ml). A significant positive correlation was found between fetal femur length at the 22nd week of gestation and maternal 25(ΟΗ)D at the 1st trimester of pregnancy (r=0.36, p=0.048) while body length was significantly higher in newborns whose mothers had sufficient 25(OH)D levels (51.5±2.1cm) compared with those whose mothers had insufficient or deficient 25(OH)D levels at delivery (50.6±2.0cm) (p=0.047). CONCLUSION: The study confirms inadequate levels of vitamin D in pregnant women in Greece associated with inadequate vitamin D levels of their fetuses and newborns.

Anemia and autoimmunity markers in an adolescent with Castleman disease.

We describe herein the case of an adolescent girl with anemia non-responsive to oral iron, associated with low-grade fever, diminished appetite and fatigue. A palpable mass below the xiphoid was noted. Laboratory findings were consistent with anemia of inflammation. Direct antiglobulin test was positive without any other evidence of autoimmune anemia. Other autoantibodies, such as anti-thyroid and anti-nuclear antibodies, were also positive. After thorough investigation, Castleman disease was the most likely diagnosis on the basis of high serum interleukin (IL)-6 and the magnetic resonance imaging findings. (18)F-FDG positron emission tomography-computed tomography showed a localized hypermetabolic mass, which was resected. Castleman disease of plasma type was identified on histology. Hemogloblin and IL-6 gradually returned to normal, whereas positive autoantibodies became negative. This case emphasizes the need to investigate thoroughly for the underlying cause of anemia of inflammation and to include Castleman disease in the differential diagnosis, on the measurement of IL-6.

Association of vitamin D receptor gene polymorphisms and vitamin D levels with asthma and atopy in Cypriot adolescents: a case-control study.

BACKGROUND: Polymorphisms in the vitamin D receptor (VDR) gene have been studied in immune-related disorders either as independent contributors or in combination with vitamin D concentration. Vitamin D and VDR have been independently linked to asthma susceptibility. We investigated whether VDR variants were associated independently or in relation to vitamin D levels with asthma in Cypriot adolescents. METHODS: We studied 190 current wheezers, 69 of which were categorized as active asthmatics and 671 healthy controls. We determined three VDR genotypes (BsmI, TaqI, ApaI) and measured serum 25(OH)D levels. Logistic regression and stratified analyses by the presence of hypovitaminosis D (≤20 ng/ml) were used to evaluate the association of the VDR variants with asthma. RESULTS: The distribution of TaqI genotypes was significantly different between controls and current wheezers (p = 0.030) or active asthmatics (p = 0.014). The tt genotype was over-represented in wheezers (19.2 %) and asthmatics (21.3 %) compared to respective controls (12.9 %). No difference was observed between controls, current wheezers and active asthmatics in the genotypic distribution of BsmI and ApaI polymorphic sites. After stratification by the presence of hypovitaminosis D, a significant association was detected between tt genotype of TaqI polymorphism with wheezing (OR: 1.97, 95 % CI: 1.12, 3.46) and asthma (OR: 2.37, 95CI%: 1.02, 5.52) only in those with normal vitamin D levels (>20 ng/ml) but not in subjects with low vitamin D. CONCLUSIONS: The minor TaqI genotype of VDR is associated with asthma in Cypriot adolescents. This polymorphism may contribute to asthma susceptibility primarily under conditions of normal vitamin D levels (>20 ng/ml).

Ultrasound imaging of the musculocutaneous nerve of infants, preschool children, and school children.

The purpose of this imaging study was to investigate whether the musculocutaneous nerve could be visualized ultrasonographically in childhood and to assess how its visualization changes with age. Forty-two children participated in this prospective imaging study. The musculocutaneous nerve was sought both proximally (near the axillary artery) and distally (within the coracobrachialis muscle) by use of an linear ultrasound probe. Location of the musculocutaneous nerve was good (93 %) for all the children, both proximally and distally. For school-aged children, distal visualization of the musculocutaneous nerve reached 100 %. The musculocutaneous nerve is detectable in childhood by use of ultrasonography; success of detection was high for all the age groups examined.

Vitamin D levels and status amongst asthmatic and non-asthmatic adolescents in Cyprus: a comparative cross-sectional study.

BACKGROUND: Emerging evidence suggests that vitamin D might be implicated in asthma pathophysiology. This study aims to compare Vitamin D mean serum levels and status between asthmatic and non-asthmatic adolescents and investigate the association of vitamin D with asthma severity. METHODS: In a cohort of adolescents aged 16-17 years, those reporting wheezing in the past 12 months and Ever asthma on the ISAAC questionnaire were invited to participate and formed the Active Asthmatics group. Controls were selected amongst Never Wheezers/Never Asthmatics (NWNA). Differences in mean 25(OH)D serum levels and vitamin D status between AA and NWNA were examined in multivariate linear and logistic regression models respectively, adjusting for potential confounders. Within AA, differences in vitamin D levels were assessed across asthma severity indicators. RESULTS: A total of 69 AA and 671 NWNA participated in the study. Unadjusted mean 25(OH)D serum levels were 22.90 (SD 6.41), and 21.15 (SD 5.59) ng/mL in NWNA and AA respectively (p = 0.03). In adjusted models, mean 25(OH)D levels remained significantly lower amongst AA compared to NWNA (adjusted beta coefficient -1.68, 95% CI -3.24, -0.13). Severe (<12 ng/mL), moderate (<25 ng/mL) or insufficient (<30 ng/mL) vitamin D status was more prevalent among AA who were 1.6 times (95% CI 1.01, 2.53) more likely to belong to a lower vitamin D category compared to NWNA. Within AA, there was a negative trend between vitamin D levels and the number of reported asthma severity indicators. CONCLUSIONS: Levels of vitamin D tend to be lower among asthmatic compared to non-asthmatic children and in those with severe asthma independent of important confounders.

Association of vitamin D with adiposity measures and other determinants in a cross-sectional study of Cypriot adolescents.

OBJECTIVE: To assess vitamin D status among Cypriot adolescents and investigate potential determinants including BMI and body fat percentage (BF%). DESIGN: Participants had cross-sectional assessments of serum vitamin D, physical activity, dietary vitamin D intake and sun exposure. Linear and logistic regression models were used to explore the associations of vitamin D with potential predictors. SETTING: Hospitals, Cyprus, November 2007-May 2008. SUBJECTS: Adolescents (n 671) aged 16-18 years. RESULTS: Mean serum vitamin D was 22·90 (sd 6·41) ng/ml. Only one in ten children had sufficient levels of vitamin D (≥30 ng/ml), while the prevalence of vitamin D deficiency (12-20 ng/ml) and severe deficiency (<12 ng/ml) was 31·7 % and 4·0 %, respectively. Lower vitamin D was associated with winter and spring season, female gender, reduced sun exposure in winter and darker skin. Participants with highest BMI and BF% when compared with a middle reference group had increased adjusted odds of vitamin D insufficiency (OR = 3·00; 95 % CI 1·21, 7·45 and OR = 5·02; 95 % CI 1·80, 13·97, respectively). A similar pattern, although not as strong, was shown for vitamin D deficiency with BF% (OR = 1·81; 95 % CI 1·04, 3·16) and BMI (OR = 1·51; 95 % CI 0·85, 2·67). Participants in the lowest BMI and BF% groups also displayed compromised vitamin D status, suggesting a U-shaped association. CONCLUSIONS: Vitamin D deficiency in adolescence is very prevalent in sunny Cyprus, particularly among females, those with darker skin and those with reduced sun exposure in winter. Furthermore, vitamin D status appears to have a U-shaped association with adiposity measures.

Identification of a novel nonsense mutation in the ligand-binding domain of the vitamin d receptor gene and clinical description of two greek patients with hereditary vitamin d-resistant rickets and alopecia.

BACKGROUND/AIMS: We analyzed the vitamin D receptor (VDR) gene in 2 Greek patients who exhibited the classical features of hereditary vitamin D-resistant rickets (HVDRR) type II, including severe bone deformities and alopecia. We also describe the clinical phenotypes and the response to treatment of our patients. METHODS: Genomic DNA was extracted from peripheral blood samples of both patients. Coding region and flanking introns of VDR gDNA was amplified and direct sequenced. RESULTS: A unique cytosine to thymine (C>T) transition was identified at nucleotide position 1066 (c.1066C>T) in the ligand-binding domain of the VDR gene of both patients, predicting the substitution of a glutamine to a terminal codon at position 356 (Gln356stop). CONCLUSIONS: The novel nonsense mutation c.1066C>T (Gln356stop) is expected to result in a VDR protein 71 amino acids shorter and thus to affect the normal VDR function. In particular, the missing protein part alters the VDR heterodimerization with the retinoid X receptor which has been correlated with the presence of alopecia. Both patients were introduced to treatment with supraphysiological doses of 1α-calcidiol which improved their clinical phenotypes except for alopecia.

Acalculous cholecystitis or biliary dyskinesia for Epstein-Barr virus gallbladder involvement?

We present two patients with Epstein-Barr virus (EBV) infection related to gallbladder involvement. Such an association is already known as EBV induced acalculous cholecystitis, diagnosed on the basis of ultrasonographic findings. In our patients, radioisotopic cholescintigraphy was also performed and it showed that gallbladder was visualized in both patients in contrast to that what can be observed in cases of cholecystitis. However, the value of ejection fraction was compatible with biliary dyskinesia. We, therefore, consider that impaired gallbladder contractility in EBV infection cases may actually represent biliary dyskinesia and not acalculous cholecystitis taking into account the radioisotopic findings and the self limited course of the disorder.

Hereditary rickets. How genetic alterations explain the biochemical and clinical phenotypes.

The reemergence of vitamin D deficiency in the industrialized countries resurrects the "threat" of nutritional rickets, especially among pediatric populations, a fact that may lead to underdiagnosis of hereditary rickets. Today, hereditary rickets may be subdivided into two main groups according to their biochemical profile: the one associated with defects in vitamin D synthesis and action and the second associated with abnormal phosphorus metabolism. The classification of the patients in a particular group of hereditary rickets is determinative of the treatment to follow. This review, through the recent advances on vitamin D and P metabolism, discusses the molecular and biochemical defects associated to each group of inherited rickets, as well as the clinical phenotypes and the recommended therapeutic approaches.

Expanding the spectrum of genetic mutations in antenatal Bartter syndrome type II.

Bartter syndrome (BS) is a group of genetic disorders characterized by hypokalemic metabolic alkalosis, hyponatremia and elevated renin and aldosterone plasma concentrations. BS type II is caused by mutations in the KCNJ1 gene and usually presents with transient hyperkalemia. We report here a novel KCNJ1 mutation in a male neonate, prematurely born after a pregnancy complicated by polyhydramnios. The infant presented with typical clinical and laboratory findings of BS type II, such as hyponatremia, hypochloremic metabolic alkalosis, severe weight loss, elevated renin and aldosterone levels and transient hyperkalemia in the early postnatal period, which were later normalized. Molecular analysis revealed a compound heterozygous mutation in the KCNJ1 gene, consisting of a novel K76E and an already described V315G mutation, both affecting functional domains of the channel protein. Typical manifestations of antenatal BS in combination with hyperkalemia should prompt the clinician to search for mutations in the KCNJ1 gene first.

Negativation of type 1 diabetes-associated autoantibodies to glutamic acid decarboxylase and insulin in children treated with oral calcitriol.

BACKGROUND: Based on recent knowledge of the possible involvement of 1,25-dihydroxyvitamin D in the pathogenesis of type 1 diabetes (T1D) and the results of its administration in animal models, we conducted a clinical trial by treating high-risk children, positive for T1D autoantibodies, with oral calcitriol. METHODS: The present prospective trial was performed on 12 children (1.5-13 years old) who were investigated for the potential risk of T1D because of an already diagnosed association of celiac disease and autoimmune thyroiditis (four girls), autoimmune thyroiditis at a very young age (two girls, two boys), a diagnosis of T1D in siblings (two boys), and impaired glucose tolerance (IGT; one boy, one girl). Serum autoantibody levels, including islet cell autoantibodies, anti-glutamic acid decarboxylase (GAD) 65, insulin autoantibodies (IAA), and anti-tyrosine phosphatase, and markers of calcium metabolism were evaluated prior to and at 6-monthly intervals after the initiation of 0.25 µg/day calcitriol for 1-3 years. RESULTS: In all children, persistent negativation of the anti-GAD65 antibodies and IAA was observed within 0.4-2.1 years. Of the two children with IGT, the boy proved to have maturity onset diabetes of the young (MODY) 2, whereas the glycemic profile was normalized in the girl. CONCLUSIONS: Despite the small number of subjects and the absence of a control group in the present study, 0.25 µg/day calcitriol effectively negativates anti-GAD65 antibodies and IAA after a median time of 6 months. This simple, safe, and low-cost strategy may prove effective in the prevention of T1D in the future.

The mediating effect of parents' educational status on the association between adherence to the Mediterranean diet and childhood obesity: the PANACEA study.

OBJECTIVES: To investigate the potential mediating effect of parental education on the association between adherence to the Mediterranean diet and obesity, in 10-12 years old children. METHODS: A cross-sectional survey was performed among 1,125 (529 male) children in Greece. Children and their parents completed standardized questionnaires, which evaluated parents' educational level and dietary habits. Body mass index was calculated and children were classified as normal, overweight or obese (IOTF classification). Adherence to the Mediterranean diet was assessed using the KIDMED score. RESULTS: 27.7% of the children were overweight and 6.3% were obese; 12.3% of children reported high adherence to the Mediterranean diet. Multi-adjusted analysis, stratified by parental education, revealed that adherence to the Mediterranean diet was inversely associated with children's obesity status only in families in which at least one parent was of higher educational level (stratum-specific adjusted odds ratio: 0.41; 95% CI 0.17-0.98), but not those in which both parents were of low educational level. CONCLUSIONS: Parental education status seems to play a mediating role in the beneficial effect of Mediterranean diet on children's obesity status.

Physical activity and exercise-induced bronchoconstriction in Greek schoolchildren.

OBJECTIVE: To investigate the association between physical activity and exercise-induced bronchoconstriction (EIB) in an urban population sample of schoolchildren, taking into account potential confounders such as asthma symptoms and overweight. METHODS: Children aged 10-12 years answered validated questionnaires on physical activity (Physical Activity and Lifestyle Questionnaire) and asthma symptoms (ISAAC questionnaire), and were categorized according to their body mass index (BMI). EIB (FEV(1) decrease from baseline ≥13%) was assessed by a standardized free running Exercise Challenge Test (ECT). RESULTS: Six hundred seven children completed the ECT. There were no differences among asthma groups (diagnosed asthma, asthma-related symptoms not diagnosed as asthma, no asthma-related symptoms) regarding total daily energy expenditure and time spent in mild (1.1-2.9 metabolic equivalents-METs), moderate (3-6 METs), and vigorous (>6 METs) activities. Only overweight/obese EIB-positive children had shorter duration of vigorous activity as compared to their EIB-negative or non-overweight/obese EIB-positive peers. Total daily energy expenditure and duration of mild- and moderate-intensity activity were negatively associated with EIB independently of BMI status or asthma-related symptoms. CONCLUSIONS: Decreased levels of physical activity are associated with EIB irrespectively of BMI status and asthma-related symptoms. Longitudinal studies are needed to confirm the negative impact of sedentary lifestyle on the development of EIB suggested by these findings.

Phenotypic spectrum of 80 Greek patients referred as Noonan syndrome and PTPN11 mutation analysis: the value of initial clinical assessment.

Noonan syndrome (NS) is a common multiple congenital anomaly entity, the diagnosis of which, on clinical grounds, is based on a comprehensive scoring system in order to select patients for molecular confirmation. Our aim was to evaluate the phenotypic characteristics in the light of PTPN11 mutations. The study revealed 80 patients who were referred with initial indication of NS or Noonan-like syndrome (NLS) and further assessed by a clinical geneticist; 60/80 index patients, mean age 5.9 ± 5.3 years, fulfilled the NS criteria. Molecular analysis of PTPN11 gene (exons and their flanking regions) of the total population revealed mutations in 17/80 patients, all belonging in the group of the patients screened with the scoring system. All mutations were heterozygous missense changes, mostly clustering in exon 3 (8/17), followed by exons 13 (3/17), 8 (2/17), 7 (2/17), 2 (1/17) and 4 (1/17). We conclude that (a) most of our clinically diagnosed NS cases were sporadic (b) PTPN11 analysis should be limited to those fulfilling the relevant NS criteria (c) Cardiovascular evaluation should comprise all NS patients, while pulmonary stenosis, short stature, and thorax deformities prevailed among those with PTPN11 mutations.

Transient elevation of the ipsilateral hemidiaphragm associated with pneumonia.

Seventeen children with lobar or segmental pneumonia and ispilateral elevation of the diaphragm are described. These children did not differ significantly with respect to clinical and laboratory findings from their counterparts with pneumonia but without elevation of the hemidiaphragm. The elevation was transient and resolved by the time the repeat chest x-ray was taken six to eight weeks later.

Is Ceftriaxone-Induced Biliary Pseudolithiasis Influenced by UDP-Glucuronosyltransferase 1A1 Gene Polymorphisms?

Ceftriaxone (cfx), a third-generation cephalosporin antibiotic, leads to transient cholelithiasis in some children, also known as pseudolithiasis. However, the underlying pathogenetic mechanism of this adverse effect has not yet been elucidated. We describe 3 children with ceftriaxone-induced pseudolithiasis, who were also carriers of the A(TA)(7)TAA polymorphism of the UGT1A1 gene, implying that a cause and effect relation may exist.

Constitutional advancement of growth is associated with early puberty in girls.

BACKGROUND: Constitutional advancement of growth (CAG) is the growth pattern of early growth acceleration that has been shown to be characteristic in girls with idiopathic precocious puberty (IPP). The aim of this study was to examine the growth pattern of girls with early puberty compared to girls with IPP. METHODS: We studied the growth pattern, from birth to presentation, of 61 girls with early puberty, of 40 girls with IPP and of 100 healthy girls with normal pubertal onset that served as controls. RESULTS: Height SDS (HSDS) at presentation was significantly different among the 3 groups (p < 0.001). Girls with early puberty were shorter than girls with IPP (HSDS 0.63 ± 1.09 vs. 0.98 ± 0.95, respectively, p < 0.001) and taller than control girls (HSDS 0.05 ± 0.94, p < 0.05). By comparing the linear growth pattern from birth to presentation, pairwise comparisons showed that it differed significantly between early puberty and control (p < 0.001) as well as between IPP and control girls (p < 0.001), whereas the difference between girls with IPP and early puberty was not significant (p = 0.09). CONCLUSION: Girls with early puberty present the pattern of CAG suggesting that IPP lies at the extreme of the distribution of the normal timing of puberty onset.

Bilateral hilar lymphadenopathy due to Chlamydia pneumoniae infection.

We here report a 5-year-old boy who presented with cough and bilateral hilar lymphadenopathy with a family history of sarcoidosis. The laboratory investigations did not confirm this diagnosis. The child was serologically proven to have Chlamydia pneumoniae infection. He responded well to a course of erythromycin resulting in complete resolution of his symptoms and the presenting radiographic findings on his initial chest X-ray. Pediatr. Pulmonol. 2011; 46:1038-1040. © 2011 Wiley-Liss, Inc.