CFTR mutational screening by next-generation sequencing reveals novel variants and a high carrier rate in a Middle Eastern population.

Cystic fibrosis is the most common life-limiting autosomal recessive disease in western countries with an incidence of 1:2500 in United States and 1:1000 in some European countries. Similar incidences were noted for the Middle East with variations from 1 in 2560 to 1 in 15,876 according to the degree of consanguinity. This is a preliminary systematic study that aims to assess the incidence and carrier rate of cystic fibrosis in the Middle Eastern Lebanese population; known for a high frequency of consanguinity. One hundred thirteen DNA samples were collected from neonatal blood cards obtained from newborns to healthy unrelated families with no previous history of Cystic fibrosis. Screening for Cystic Fibrosis-causing pathogenic variants was performed using next generation sequencing, and 17 different single nucleotide variants were detected, including six pathogenic and likely pathogenic. 5.5%-7% newborns were found to be carriers of a variant strongly suggestive of pathogenicity and comparable to published literature worldwide. This pilot analysis highlights the challenging interpretation of CFTR variants in a country underrepresented by large ethnic population analyses, and stresses the importance of premarital screening programs for Cystic fibrosis.

The Spectrum of ß-Thalassemia Mutations in the Population Migration in Lebanon: A 6-Year Retrospective Study.

ß-Thalassemia (ß-thal) is highly prevalent among the Mediterranean populations. In Lebanon, the carrier rate of the disease is estimated to be around 2.0-3.0%. In this retrospective study, we determined the spectrum of ß-thal mutations in a total of 170 individuals from a sample of 140 Lebanese, Iraqi and Syrian refugee families in Lebanon, over a period from 2012 to 2018. Twenty-eight different ß-globin gene mutations were identified. The most prevalent mutations were IVS-I-110 (G>A) (HBB: c.93-21G>A), IVS-II-1 (G>A) (HBB: c.315+1G>A), IVS-I-6 (T>C) (HBB: c.92+6T>C) and IVS-I-1 (G>A) (HBB: c.92+1G>A), accounting for the majority of mutations found in HBB mutations analysed in 250 alleles. Ten different ß-globin gene mutations that were not previously described in Lebanon were identified in our study. These mutations include the IVS-II-848 (C>A) (HBB: c.316-3C>A), codons 9/10 (+T) (HBB: c.30_31insT), codon 15 (-T) (HBB: c.46delT), -86 (C>G) (HBB: c.-136C>G), Cap +22 (G>A) (HBB: c.-29G>A), -28 (A>C) (HBB: c.-78A>C), codon 7 (GAG>TAG) (HBB: c.22G>T), codon 26 (GAG>TAG) (HBB: c.79G>T), codons 41/42 (-TTCT) (HBB: c.126_129delCTTT), and codons 82/83 (-G) (HBB: c.250delG). Of these, six mutations [codons 9/10, codon 15 (-T), -86, codon 7, codon 26, codons 82/83) were identified in Lebanese samples only; one mutation (IVS-II-848) was identified in both Lebanese and Iraqis; and three mutations (Cap +22, -28, codons 41/42) were identified in Iraqi samples only. Further studies will help better delineate the spectrum of ß-thal mutations among different ethnic groups, and provide crucial prevention strategies.

Transcutaneous embolisation of an axillary artery aneurysm in a child with Takayasu arteritis.

We report the case of a 10-year-old girl with Takayasu arteritis who developed acute onset wrist drop diagnosed with a large right axillary artery aneurysm compressing the surrounding structures. Our case is unique because it describes a rare presentation of Takayasu arteritis (axillary aneurysm) in a child that was treated successfully in an unconventional manner by transcutaneous embolisation following failure of trans-arterial approach.

Questionnaire-based survey in a developing country showing noncompliance with paediatric gastro-oesophageal reflux practice guidelines.

AIM: This 2015 study investigated whether Lebanese paediatricians diagnosed and managed gastro-oesophageal reflux disease (GERD) in infants and children in accordance with the 2009 guidelines from the North American and European Societies for Paediatric Gastroenterology, Hepatology and Nutrition. METHODS: Paediatricians members of the Lebanese Order of Physicians with updated email addresses were invited to complete a web-based survey between September and November 2015, to assess their knowledge and management of GERD. RESULTS: Responses were received from 114 of the 543 paediatricians, and 96 were analysed. Only two respondents complied fully with the international guidelines. The majority diagnosed GERD in infants based solely on their medical history and examination. Moreover, nearly two-thirds of the respondents would start an empiric trial with acid suppression. Around half of the respondents considered proton pump inhibitors to be the mainstay of GERD treatment. CONCLUSION: This was the first Lebanese study that surveyed the management of paediatric GERD. Only 2.1% of the paediatricians followed the guidelines on the evidence-based management of GERD. This highlights the need for studies to assess barriers to guideline implementation and the development of new guidelines accounting for regional factors, mainly the cost of investigations and prevalence of medical insurance.

Effect of Malnutrition at Diagnosis on Clinical Outcomes of Children With Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is the most common malignancy among children. Although studies have shown that malnutrition can negatively affect treatment outcome, results are controversial. This retrospective study aims at determining the prevalence of malnutrition and its association with treatment outcome among children with ALL treated at the Children's Cancer Institute in Lebanon. A total of 103 patients diagnosed with ALL between April 2002 and May 2010 were enrolled. Anthropometric data were collected from medical records upon diagnosis, at 3 and 6 months, and at the end of treatment. Body mass index was calculated for children 2 years of age and older, whereas weight-for-height ratio was used for patients below 2 years. Patients were considered underweight, stunted, or wasted if their Z-scores were <-2 SD. The prevalence of malnourished children was 25.2% at diagnosis and remained almost the same at the end of treatment. The odds of having a poor outcome (death and relapse) was higher among malnourished children and more so among stunted children with an odds ratios=2.15; 95% confidence interval, 0.5-8.3 and odds ratio=2.63; 95% confidence interval, 0.6-11.5, respectively. Although there was a trend showing worse outcomes in malnourished children with ALL at diagnosis when compared with well-nourished children larger studies using additional tools like arm anthropometry need to be conducted to prove the association.

Validity and reliability of a food frequency questionnaire to estimate dietary intake among Lebanese children.

BACKGROUND: Nutritional status during childhood is critical given its effect on growth and development as well as its association with disease risk later in life. The Middle East and North Africa (MENA) region is experiencing alarming rates of childhood malnutrition, both over- and under-nutrition. Hence, there is a need for valid tools to assess dietary intake for children in this region. To date, there are no validated dietary assessment tools for children in any country of the MENA region. The main objective of this study was to examine the validity and reliability of a Food Frequency Questionnaire (FFQ) for the assessment of dietary intake among Lebanese children. METHODS: Children, aged 5 to 10 years (n = 111), were recruited from public and private schools of Beirut, Lebanon. Mothers (proxies to report their children's dietary intake) completed two FFQs, four weeks apart. Four 24-hour recalls (24-HRs) were collected weekly during the duration of the study. Spearman correlations and Bland-Altman plots were used to assess validity. Linear regression models were used to derive calibration factors for boys and girls. Reproducibility statistics included Intraclass Correlation Coefficient (ICC) and percent agreement. RESULTS: Correlation coefficients between dietary intake estimates derived from FFQ and 24-HRs were significant at p < 0.001 with the highest correlation observed for energy (0.54) and the lowest for monounsaturated fatty acids (0.26). The majority of data points in the Bland-Altman plots lied between the limits of agreement, closer to the middle horizontal line. After applying the calibration factors for boys and girls, the mean energy and nutrient intakes estimated by the FFQ were similar to those obtained by the mean 24-HRs. As for reproducibility, ICC ranged between 0.31 for trans-fatty acids and 0.73 for calcium intakes. Over 80 % of study participants were classified in the same or adjacent quartile of energy and nutrients intake. CONCLUSIONS: Findings of this study showed that the developed FFQ is reliable and is also valid, when used with calibration factors. This FFQ is a useful tool in dietary assessment and evaluation of diet-disease relationship in this age group.

Dietary Zinc Intake and Plasma Zinc Concentrations in Children with Short Stature and Failure to Thrive.

BACKGROUND: The burden of zinc deficiency on children includes an increased incidence of diarrhea, failure to thrive (FTT) and short stature. The aim of this study was to assess whether children with FTT and/or short stature have lower dietary zinc intake and plasma zinc concentrations compared to controls. METHODS: A case-control study conducted at the American University of Beirut Medical Center included 161 subjects from 1 to 10 years of age. RESULTS: Cases had a statistically significant lower energy intake (960.9 vs. 1,135.2 kcal for controls, p = 0.010), lower level of fat (30.3 vs. 36.5 g/day, p = 0.0043) and iron intake (7.4 vs. 9.1 mg/day, p = 0.034). There was no difference in zinc, copper, carbohydrate and protein intake between the 2 groups. The plasma zinc concentration did not differ between the cases and controls (97.4 vs. 98.2 µg/dl, p = 0.882). More cases had mild-to-moderate zinc deficiency when compared to controls with 10.3 vs. 3.6%, p = 0.095. CONCLUSION: Our study did not show statistically significant difference in dietary zinc intake and plasma zinc concentrations between children with FTT and/or short stature compared to healthy controls. A prospective study is planned to assess the effect of zinc supplementation on growth parameters in FTT children.

Mitochondrial depletion syndrome type 3: the Lebanese variant.

Introduction: Mitochondrial DNA depletion syndrome type 3 is an emerging disorder linked to variants in the deoxyguanosine kinase gene, which encodes for mitochondrial maintenance. This autosomal recessive disorder is frequent in the Middle East and North Africa. Diagnosis is often delayed due to the non-specificity of clinical presentation with cerebro-hepatic deterioration. The only therapeutic option is liver transplantation, although the value of this remains debatable. Methods: We describe the clinical, biochemical, and molecular profiles of Lebanese patients with this rare disorder. We also present a review of all cases from the Middle East and North Africa. Results: All Lebanese patients share a unique mutation, unreported in other populations. Almost half of patients worldwide originate from the Middle East and North Africa, with cases reported from only 7 of the 21 countries in this region. Clinical presentation is heterogeneous, with early-onset neurological and hepatic signs. Liver failure and lactic acidosis are constants. Several variants can be identified in each population; a unique c.235C>T p. (Gln79*) pathogenic variant is found in Lebanese patients. Outcome is poor, with death before 1 year of age. Conclusion: The pathogenic nonsense variant c.235C>T p. (Gln79*) in the deoxyguanosine kinase gene may be considered a founder mutation in Lebanon. Further genotypic delineation of this devastating disorder in populations with high consanguinity rates is needed.

Knowledge, attitudes, and practices of pediatricians in relation to breastfeeding support: A national survey in Lebanon.

BACKGROUND: Rates of breastfeeding (BF) remain suboptimal despite overwhelming evidence for its benefits to the mother and child. Pediatricians play an important role in supporting breastfeeding (BF). In Lebanon, the rates of both exclusive and continued BF are critically low. The objective of this study is to examine the knowledge, attitudes and practices (KAP) of Lebanese pediatricians in relation to supporting BF. METHODS: A national survey of Lebanese pediatricians was conducted through Lime Survey (n = 100, response rate 9.5%). The list of pediatricians' emails was obtained from the Lebanese Order of Physicians (LOP). Participants completed a questionnaire covering, in addition to sociodemographic characteristics, the KAP, related to supporting BF. Descriptive statistics and logistic regressions were used in data analysis. RESULTS: The most prevalent gaps in knowledge were related to the positioning of the baby during BF (71.9%) and the association between the mother's fluid intake and her milk production (67.4%). With regards to attitudes, 34% of participants reported unfavorable attitudes towards BF in public and BF while working (25%). As for practices, more than 40% of pediatricians kept formula samples and 21% had formula-related advertising in their clinics. Half of the pediatricians reported rarely/never referring mothers to lactation consultants. After adjustment, both being a female pediatrician and having done the residency in Lebanon were significant predictors of better knowledge (OR = 4.51 (95%CI: 1.72-11.85) and OR = 3.93 (95%CI: 1.38,11.19) respectively. CONCLUSION: This study revealed important gaps in the KAP related to BF support among Lebanese pediatricians. Coordinated efforts ought to be exerted to educate and equip pediatricians with needed knowledge and skills to support BF.

A Congenital Choledochal Cyst in an Adolescent: A Unique Case Report and the Role Liver-Specific Contrast Agents in the Diagnosis of Challenging Cases.

Choledochal cysts are rare congenital cystic dilatations of the biliary tree. They are most commonly present in female infants and young children, and their pathology remains unclear. The triad of intermittent jaundice, abdominal mass, and pain is found only in a minority of patients. Diagnosis and delineation of accurate biliary anatomy are crucial for surgical planning. This is most often successfully achieved with ultrasound and magnetic resonance cholangiopancreatography. The definitive treatment is cyst excision which decreases the risk of biliary carcinoma. We present an unusual case of a choledochal cyst in an adolescent boy with a review of the literature and emphasis on multi-imaging modalities, including the role of liver-specific gadolinium contrast agents in challenging cases to confirm the diagnosis.

Intestinal polypoid arteriovenous malformation: unusual presentation in a child and review of the literature.

AIM: We report a jejuno-jejunal intussusception with a polypoid arteriovenous malformation as a lead point in a 12-year-old boy, presenting with lower abdominal pain and non-bloody non-projectile vomiting. METHODS: A computed tomography scan of the abdomen and pelvis showed proximal jejuno-jejunal intussusception in the right upper quadrant. Exploratory laparotomy revealed a 5.5 × 2.5 × 2 cm polypoid mass within the wall of the jejunum. Consequently, jejunal segment resection was performed with end to end jejunostomy. Our case is distinctive because it involves a rare vascular lesion at an atypical site, the jejunum, in a child with an unusual presentation of intussusception treated surgically. CONCLUSION: Many paediatric benign and surgical conditions present with similar clinical symptoms; the physician in the emergency department should try to narrow the differential diagnosis and recognize surgical emergencies to avoid any delay in intervention that could be life-threatening.

Goldenhar syndrome associated with prenatal maternal Fluoxetine ingestion: Cause or coincidence?

Goldenhar syndrome, also known as oculo-auriculo-vertebral spectrum, is a complex, heterogeneous condition characterized by abnormal prenatal development of facial structures. We present the occurrence of Goldenhar syndrome in an infant born to a woman with a history of prenatal Fluoxetine ingestion throughout her pregnancy. Because this is the first reported case associating maternal Fluoxetine intake with fetal craniofacial malformations, a potential mechanism of injury is discussed. The propositus, a male born from nonconsanguinous parents, had facial asymmetry with right microtia and mandibular hypoplasia; he also had bilateral hypoplastic macula, scoliotic deformity of the thoracic spine, and ventricular septal defect. The mother was under treatment with Fluoxetine 20 mg/day prior to conception and maintained the same dosage throughout her pregnancy. The drug is a selective serotonin re-uptake inhibitor, the most widely prescribed for the treatment of depression. The occurrence of developmental aberrations may be caused by a profound serotonin receptor suppressive state in utero leading to aberrant clinical manifestations of the first and second branchial arches. Despite the very many limitations of case reporting of teratogenic events, it remains an important source of information on which more advanced research is based.

A young child with HIV and unsteady gait: A case report.

BACKGROUND: We would like to raise awareness about the toxicities related to the added excipients present in the oral solution of Liponavir/ritonavir in particular alcohol and propylene glycol. CASE PRESENTATION: In this case report, we describe an 18 month-old child with a newly diagnosed HIV infection on antiretroviral therapy (ART). She developed shortly after starting the ART unsteady gait and imbalance. CONCLUSIONS: The excipient-excipient interaction in Lopinavir/ritonavir may contribute to major toxicities not only in premature neonates and infants; but also in older children specifically from Asian ethnicity.

Effect of a Quality Improvement Project to Reduce Noise in a Pediatric Unit.

PURPOSE: Noise levels remain high in clinical settings, which may result in stress and sleep disruption, and can lead to immunosuppression, delayed healing, confusion, disorientation, delusions, and increased length of hospital stay. The purpose of this quality improvement project was to assess effects of a multidisciplinary noise reduction program on a pediatric unit in an acute care hospital in a developing country. METHODS: A quality improvement project was carried out over 15 months in a pediatric unit. A three-phase study was conducted where the first phase included obtaining patient satisfaction ratings and recording sound levels, the second phase included implementing a noise reduction program and designing a noise detector machine, and the third phase included obtaining patient satisfaction data and recording noise levels over a 1-year period. RESULTS: There was a significant decrease in noise of 8 A-weighted decibels when comparing the values before and after implementing the quality improvement project at t = 6.44, p < 0.000. There was no significant difference in patient satisfaction ratings. CLINICAL IMPLICATIONS: Noise in the pediatric unit exceeded recommended guidelines; however, decreasing the levels was possible and sustainable, which can improve the psychological and physiological wellbeing of hospitalized children.

Lactose-free milk for infants with acute gastroenteritis in a developing country: study protocol for a randomized controlled trial.

BACKGROUND: Acute gastroenteritis is a major cause of pediatric morbidity and mortality, accounting for 15% of all childhood deaths worldwide. In developing countries, diarrheal diseases continue to be a major public health burden. Evidence from developed countries suggests that intake of lactose-free milk during diarrheal episodes may reduce the duration of the illness in pediatric inpatients. It is unknown whether lactose-free milk reduces the severity or duration of acute gastroenteritis in infants treated in outpatient settings in developing countries where diarrhea is more severe, and results in higher morbidities and mortalities. We hypothesize that lactose-free milk intake during acute gastroenteritis would significantly decrease the duration and severity of diarrhea in infants presenting to the Emergency Department (ED), as compared with lactose-containing milk. METHODS/DESIGN: An open-label randomized clinical trial. STUDY POPULATION: 40 infants with acute gastroenteritis, age between 2 and 12 months, presenting to the ED, will be randomized to control or intervention group. INTERVENTION: Lactose-free milk, whereas the control group will continue on regular infant formula for a total of 7 days. Infants will be followed up for 7 days. OUTCOME MEASURES: Diarrhea duration, weight loss, illness clinic visits, hospitalization rate, parental satisfaction, and time to symptom resolution. STATISTICAL ANALYSIS: Descriptive and regression analysis will be conducted under the intention-to-treat basis by using SPSS version 21. DISCUSSION: Acute gastroenteritis is a public health burden for developing countries, with a significant impact on infant morbidity and mortality. Provision of infant formula that may reduce the duration and severity of diarrhea can decrease this burden in countries with limited healthcare resources, like Lebanon. The findings from this study are anticipated to provide evidence-based dietary recommendations for ambulatory infants with acute diarrhea in developing countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT02246010; September 2014.

Ellis-van Creveld Syndrome: Mutations Uncovered in Lebanese Families.

Background. Ellis-van Creveld (EvC) syndrome is a rare, autosomal recessive disorder characterized by short stature, short limbs, growth retardation, polydactyly, and ectodermal defects with cardiac anomalies occurring in around 60% of cases. EVC syndrome has been linked to mutations in EVC and EVC2 genes. Case Presentation. We report EvC syndrome in two unrelated Lebanese families both having homozygous mutations in the EVC2 gene, c.2653C>T (p.(Arg885(*))) and c.2012_2015del (p.(Leu671(*))) in exons 15 and 13, respectively, with the latter being reported for the first time. Conclusion. Although EvC has been largely described in the medical literature, clinical features of this syndrome vary. While more research is required to explore other genes involved in EvC, early diagnosis and therapeutic care are important to achieve a better quality of life.

Dubowitz syndrome: common findings and peculiar urine odor.

BACKGROUND: Dubowitz syndrome is a rare, autosomal recessive disorder characterized by intrauterine and postnatal growth retardation, severe microcephaly, psychomotor retardation, hyperactivity, eczema, and characteristic dysmorphic facial features. Although many cases have been reported, the cause of this disease is still unknown. CASE: We present here the case of a Lebanese girl with Dubowitz syndrome in whom an unpleasant urine odor was persistently reported since birth. CONCLUSION: Although Dubowitz syndrome has been largely described in the medical literature, this is the first time that a peculiar urine odor was reported. This case report adds a new and unusual feature to the numerous findings related to this rare polymorphous syndrome.