Clinical characteristics and liver profiles of Dubin-Johnson syndrome in neonates: Multicenter retrospective study.

OBJECTIVES: Dubin-Johnson syndrome (DJS) is a rare benign autosomal recessive disorder characterized by cholestasis in neonates. The aim of the present study was to describe the clinical characteristics, hepatic profiles, histopathology, gene mutations, and treatment outcomes of neonatal DJS. MATERIAL AND METHODS: A multicenter retrospective study was undertaken with patients who had DJS. The authors identified DJS in neonates and reviewed medical records for details. The diagnosis of DJS was based on the presence of unexplained prolonged conjugated hyperbilirubinemia and presence of a mutation in the ATP Binding Cassette Subfamily C Member 2 (ABCC2) gene detected in genomic DNA extracted from circulating blood cells. RESULTS: Eleven children with DJS were identified in the study. The study population comprised eight males and three females. The median age at presentation was 21 days. Dysmorphic features were not recorded in any of the patients. Cholestasis, high serum bile acids, and normal transaminase levels were found in all patients (100%). Serum alkaline phosphatase and gamma glutamyl transferase were elevated in four patients (36%). Hypoalbuminemia and coagulopathy were not noted in these patients. Consanguinity was present in nine patients (82%). All patients had normal abdominal ultrasound findings. Genetic molecular testing showed that 82% of the patients reported a pathogenic variant of the ABCC2 gene defect with the same variant c.2273G>T (Gly 758 val) chromosome 10. All patients were alive without liver transplantation. CONCLUSIONS: This is the largest study worldwide describing that neonatal DJS is a benign cholestatic disease with favorable outcomes. Low-grade direct hyperbilirubinemia, normal transaminases, and elevated serum bile acids are the main characteristic findings of DJS.

Char Syndrome a novel mutation and new insights: A clinical report.

Transcription Factor AP-2 Beta (TFAP2B) functions in the differentiation of neural crest cell derivatives and contributes to the embryogenesis of the ductus arteriosus. Mutations of TFAP2B produces Char syndrome. Char syndrome is an autosomal dominant disorder comprising facial dysmorphism, hand anomalies, and patent ductus arteriosus (PDA). In this report, we describe a proband with a de novo TFAP2B frameshift mutation c.650delG p.(Gly217Alafs*32) in the basic domain. The proband presented mainly with musculoskeletal features of Char syndrome. No PDA was identified at presentation suggesting that this syndrome may prove to be phenotypically heterogeneous. This report will help illustrate the genotype/phenotype correlation of TAFB2 mutations and better delineate the clinical features in Char syndrome.

In vitro assessment of ribose modified two-step etch-and-rinse dentine adhesive.

OBJECTIVE: Collagen fibrils aid in anchoring resin composite restorations to the dentine substrate. The aim of the study was to investigate effect of non-enzymatic glycation on bond strength and durability of demineralized dentine specimens in a modified two-step etch-and-rinse dentine adhesive. METHODS: Dentine surfaces were etched with 37% phosphoric acid, bonded with respective in vitro ethanol and acetone adhesives modified with (m/m, 0, 1%, 2% and 3% ribose), restored with restorative composite-resin, and sectioned into resin-dentine slabs and beams to be stored for 24h or 12 months in artificial saliva. Bond-strength testing was performed with bond failure analysis. Pentosidine assay was performed on demineralized ribose modified dentine specimens with HPLC sensitive fluorescent detection. The structural variations of ribose-modified dentine were analysed using TEM and human dental pulpal cells were used for cell viability. Three-point bending test of ribose-modified dentine beams were performed and depth of penetration of adhesives evaluated with micro-Raman spectroscopy. The MMP-2 and cathepsin K activities in ribose-treated dentine powder were also quantified using ELISA. Bond strength data was expressed using two-way ANOVA followed by Tukey's test. Paired T tests were used to analyse the specimens for pentosidine crosslinks. The modulus of elasticity and dentinal MMP-2 and cathepsin K concentrations was separately analyzed using one-way ANOVA. RESULTS: The incorporation of RB in the experimental two-step etch-and-rinse adhesive at 1% improved the adhesive bond strength without adversely affecting the degree of polymerisation. The newly developed adhesive increases the resistance of dentine collagen to degradation by inhibiting endogenous matrix metalloproteinases and cysteine cathepsins. The application of RB to acid-etched dentine helps maintain the mechanical properties. SIGNIFICANCE: The incorporation of 1%RB can be considered as a potential candidate stabilizing resin dentine bond.

Effect of vitamin D replacement on maternal and neonatal outcomes: a randomised controlled trial in pregnant women with hypovitaminosis D. A protocol.

INTRODUCTION: The vitamin D recommended doses during pregnancy differ between societies. The WHO guidelines do not recommend routine prenatal supplementation, but they underscore the fact that women with the lowest levels may benefit most. The effects of routine supplementation during pregnancy on maternal and neonatal clinical outcomes have not been investigated in the Middle East, where hypovitaminosis D is prevalent. Our hypothesis is that in Middle Eastern pregnant women, a vitamin D dose of 3000 IU/day is required to reach a desirable maternal 25-hydroxyvitamin D [25(OH)D] level, and to positively impact infant bone mineral content (BMC). METHODS AND ANALYSIS: This is a multicentre blinded randomised controlled trial. Pregnant women presenting to the Obstetrics and Gynaecology clinics will be approached. Eligible women will be randomised to daily equivalent doses of cholecalciferol, 600 IU or 3000 IU, from 15 to 18 weeks gestation until delivery. Maternal 25(OH)D and chemistries will be assessed at study entry, during the third trimester and at delivery. Neonatal anthropometric variables and 25(OH)D level will be measured at birth, and bone and fat mass assessment by dual-energy X-ray absorptiometry scan at 1 month. A sample size of 280 pregnant women is needed to demonstrate a statistically significant difference in the proportion of women reaching a 25(OH)D level ≥ 50 nmol/L at delivery, and a difference in infant BMC of 6 (10)g, for a 90% power and a 2.5% level of significance. The proportions of women achieving a target 25(OH)D level will be compared between the two arms, using χ(2). An independent t test will be used to compare mean infant BMC between the two arms. The primary analysis is an intention-to-treat analysis of unadjusted results. ETHICS AND DISSEMINATION: The protocol has been approved by the Institutional Review Board at the American University of Beirut-Lebanon (IM.GEHF.22). The trial results will be published in peer-reviewed medical journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: NCT02434380.

Predictors of trabecular bone score in school children.

UNLABELLED: Trabecular bone score (TBS) is a DXA-based tool that assesses bone texture and reflects microarchitecture. It has been shown to independently predict the risk of osteoporotic fracture in the elderly. In this study, we investigated the determinants of TBS in adolescents. INTRODUCTION: TBS is a gray-level textural measurement derived from lumbar spine DXA images. It appears to be an index of bone microarchitecture that provides skeletal information additional to the standard BMD measurement and clinical risk factors. Our objectives were to characterize the relationship between TBS and both age and pubertal stages and identify other predictors in adolescents. METHODS: We assessed TBS by reanalyzing spine DXA scan images obtained from 170 boys and 168 girls, age range 10-17 years, gathered at study entry and at 1 year, using TBS software. The results are from post hoc analyses obtained using data gathered from a prospective randomized vitamin D trial. Predictors of TBS were assessed using t test or Pearson's correlation and adjusted using regression analyses, as applicable. RESULTS: The mean age of the study population was 13.2 ± 2.1 years, similar between boys and girls. Age, height, weight, sun exposure, spine BMC and BMD, body BMC and BMD, and lean and fat mass are all significantly correlated with TBS at baseline (r = 0.20-0.75, p < 0.035). Correlations mostly noted in late-pubertal stages. However, after adjustment for BMC, age remained an independent predictor only in girls. CONCLUSIONS: In univariate exploratory analyses, age and pubertal stages were determinants of TBS in adolescents. Studies to investigate predictors of TBS and to investigate its value as a prognostic tool of bone fragility in the pediatric population are needed.

Impact of maternal veiling during pregnancy and socioeconomic status on offspring's musculoskeletal health.

UNLABELLED: The impact of maternal veiling during pregnancy and of socioeconomic status on offspring's bone mass was investigated in 326 healthy adolescents. Veiling during pregnancy was associated with decreased musculoskeletal parameters in the offspring boys, but not girls. SES was a significant predictor of bone mass in both genders. INTRODUCTION: This study investigates the effects of maternal veiling during pregnancy, a surrogate for low vitamin D level, and socioeconomic status (SES), a surrogate of nutritional status, on their offspring's bone mass at adolescence. METHODS: Three hundred and twenty-six healthy adolescents aged 13.1(2.0) years and their mothers were studied. The impact of maternal veiling on offspring's bone mass was evaluated through regression analyses. Outcome variables were bone mineral density (BMD) and content (BMC) at the spine, hip, and total body of the children. Predictors were maternal veiling during pregnancy and SES. Covariates were height, body composition, Tanner staging, calcium intake, vitamin D and exercise in children. RESULTS: In boys, adjusted analyses revealed that both maternal veiling during pregnancy and SES were significant predictors of bone mass, at multiple skeletal sites. In girls, SES but not maternal veiling during pregnancy was a significant predictor of bone mass at multiple sites. CONCLUSION: Maternal veiling during pregnancy was associated with decreased musculoskeletal parameters of boys, but not girls. SES was a significant predictor of bone mass in both genders. These findings may have profound implications on children's bone health.

Low calcium and vitamin D intake in healthy children and adolescents and their correlates.

BACKGROUND: Optimal dietary calcium and possibly vitamin D intake throughout childhood and adolescence may enhance bone mineral accrual. Little data on the intake of these nutrients in Mediterranean countries exist, and predictors of their suboptimal intake are not well defined. OBJECTIVE: To evaluate systematically the effect of gender, lifestyle factors, and socioeconomic status on mean calcium and vitamin D intake in healthy school children and adolescents from Lebanon. DESIGN: A total of 385 students aged 10-16 y were selected from four public and four private schools between Fall 1999 and Spring 2000. Information on calcium and vitamin D intake, through a semiquantitative food frequency questionnaire that was validated against a 7-day daily record, and on socioeconomic and lifestyle factors were obtained. RESULTS: Only 12% of the students met the adequate intake (AI) recommendation of 1300 mg of calcium/day, and only 16% met the AI recommendation of 200 IU of vitamin D/day. Boys had a significantly higher mean daily calcium intake than girls. Socioeconomic status as assessed by children's pocket money was a predictor of higher calcium and vitamin D intake. Eating breakfast and physical activity were other correlates of daily calcium and vitamin D intake. CONCLUSIONS: Only a minority of students in our study met the AI for calcium and vitamin D. Gender, lifestyle factors, and socioeconomic status were significant predictors of calcium and vitamin D intake. Our findings have important implications regarding the institution of dietary public health strategies to promote skeletal health in Mediterranean countries during a critical time for bone mass accrual.

Attitudes towards prenatal diagnosis and termination of pregnancy among health professionals in Lebanon.

OBJECTIVES: To assess the attitudes of health professionals in Lebanon towards prenatal diagnosis and termination of pregnancy, for a series of genetic, non-genetic and non-medical conditions. METHODS: A total of 158 questionnaires were sent to geneticists, family doctors, pediatricians and obstetricians/gynecologists, that included information on sociodemographic variables and sets of questions and case scenarios, to which participants were asked to reply anonymously. RESULTS: Responses from the 75 participants revealed that the type of specialty did not significantly influence their attitude. However, acceptance of termination of pregnancy was influenced by gender, age, marital status, religion and its importance in their daily life. In general, acceptance of termination of pregnancy in the case of mild or severe clinical conditions was comparable to that reported from European countries, but more favorable in the case of sex chromosome abnormalities. Acceptance of prenatal diagnosis for non-clinical conditions was, however, lower than that reported in Western nations. CONCLUSION: The study provides a good basis for further studies with a larger number of respondents representing various geographical regions of the country.

Prevalence of hepatitis B infection markers in Lebanese children: the need for an expanded programme on immunization.

This multi-centre, cross-sectional study was designed to reveal the present status of hepatitis B infection markers among Lebanese children, and provide recommendations regarding childhood immunization policies. A total of 841 children, aged between 6 months and 6.5 years, were enrolled from Lebanon's five districts. Their sera were tested for hepatitis B surface antigen and hepatitis B core IgG. The overall prevalence of hepatitis B virus infection markers was 0.8% with increasing age-specific rates from 0% at 6 months to 1.3 % at > 5 years. There was no statistically significant association between the presence of hepatitis B markers and family characteristics or risk factors for infection. The highest prevalence rates were among children from Beirut suburbs (2.9 %) and South Lebanon (1.6%). The risk of horizontal transmission of hepatitis B to uninfected children increased substantially after the age of 2 years. An expanded programme on immunization that integrates hepatitisB vaccine during the first year of life is needed.

Hypovitaminosis D in healthy schoolchildren.

BACKGROUND: Vitamin D is essential for skeletal growth, but there are currently no guidelines for vitamin D supplementation after infancy. This study investigates vitamin D insufficiency in healthy children. METHODS: Children ages 10 to 16 years from 3 private schools in Beirut, Lebanon, with differing socioeconomic status (SES) were studied: 169 in the spring of 1999 and 177 in the following fall; 83 students participated in both study phases. They had a physical examination, answered a dietary questionnaire, and blood was drawn for calciotropic hormones and indices of bone turnover. RESULTS: Overall, 52% of the students were vitamin D-insufficient; the proportion of insufficiency was 65% in the winter and 40% at the end of the summer. During both seasons, girls had lower vitamin D levels than did boys; those who followed the dress code of covered head, arms, and legs had the lowest levels. Students in the mid-SES school had lower 25-hydroxyvitamin D (25-OHD) levels than did the ones from the high-SES school. After adjusting for confounders, gender, SES, and body mass index remained the significant predictors of vitamin D levels in both seasons (R(2) = 0.53, for spring and 0.28 for fall). There was a significant inverse correlation between 25-OHD levels and parathyroid hormone levels that was best fitted by a curvilinear model (R(2) = 0.19). CONCLUSION: Even in a sunny country, hypovitaminosis D is common in schoolchildren, more so in the winter. Girls, especially those with a lower SES, are at particular risk. The inverse changes in parathyroid hormone suggest that insufficient vitamin D levels may deleteriously affect skeletal metabolism in healthy adolescents. Vitamin D insufficiency may be prevalent in many other countries where supplementation of milk with vitamin D is not mandatory. Our results call to a reconsideration of vitamin D supplementation in high-risk adolescents to further optimize skeletal health. vitamin D insufficiency, bone metabolism, nutrition, gender, socioeconomic status.

Beta-thalassemia mutations and haplotype analysis in Lebanon.

The molecular basis of beta-thalassemia in Lebanon reflects the heterogeneity of the Lebanese population. Eighteen different mutations were identified among a total of 277 chromosomes. There is evidence of clustering of some mutations in particular geographic regions or among specific religious groups. Haplotype analysis, using seven restriction sites was performed on a total of 110 samples and 11 different haplotypes were identified. The five most common mutations were each found on two different haplotypes, and most linkages were as previously reported in other Mediterranean populations, with a few exceptions, also showing some clustering.

Acceptance of prenatal diagnosis for genetic disorders in Lebanon.

Acceptance of prenatal diagnosis and termination of pregnancy in the case of an affected fetus may vary from one country to another, depending on the health system, religious belief, cultural and educational backgrounds of the population. Following a previous study on couples at risk for a haemoglobin disorder in Lebanon, we have here interviewed 90 couples at risk for a variety of genetic disorders, in order to assess their acceptance of prenatal diagnosis and the variables that might influence their choice. Overall, 54 per cent of couples said they would request diagnosis in their next pregnancy, while 26 per cent were opposed to such a procedure. In 87. 5 per cent of cases, the reason for refusal was because of religious conviction against termination of pregnancy. Refusal of prenatal diagnosis was also related to a lower socio-economic background and poorer education. Only 12 per cent of couples were properly aware of their genetic risk. Therefore, for prevention of genetic disorders, the emphasis in countries such as Lebanon has probably to be placed on public awareness about genetic risks, the risks of consanguinity, availability of services, while taking into consideration the personal beliefs of the individuals.

Down syndrome in two siblings with 47,XY,+21 and 46,XY/46,XY,-21,+t(21q;21q).

This is the first report in the literature of siblings affected with Down syndrome; one sibling had a nondisjunction of chromosome 21 and the other a (21q;21q) translocation.