Vitamin D deficiency might contribute to the pathogenesis of metabolic syndrome and could cause immune disturbance. The aim of this study is to analyze the associations between Vitamin D receptor (VDR) gene polymorphism, serum 25-hydroxy vitamin D, metabolic and inflammatory biomarkers in Egyptian obese women. The study included 201 obese women with vitamin D deficiency and 249 obese matched age healthy controls with sufficient vitamin D levels. Their age ranged between 25 and 35 years. Inflammatory biomarkers (interleukin-6 and C-reactive protein) and serum 25(OH) D were measured by enzyme-linked immunosorbent assay. Insulin resistance (IR) was determined by the homeostasis model assessment of insulin resistance (HOMA-IR).Vitamin D receptor (VDR) gene polymorphisms of FokI, ApaI, and TaqI were studied by PCR using the restriction fragment length polymorphism (RFLP) technique. Obese women with vitamin D deficiency had significant higher values of inflammatory and metabolic parameters compared to controls. Multivariable-logistic regression showed associations between 25(OH) D deficiency and metabolic components when comparing cases with controls. Moreover, cases carrying polymorphic alleles showed significant lower levels of serum 25(OH) D and higher HOMA-IR, blood pressure levels and lipid parameters compared to those with the wild type homozygote in obese cases with vitamin D deficiency. Vitamin D deficiency in Egyptian obese women with vitamin D deficiency is associated with abnormal metabolic components and abnormal inflammatory biomarkers. Moreover, VDR polymorphisms play important role in immune and inflammation status.

Aim Molybdenum cofactor deficiency (MoCD) and Sulfite oxidase deficiency (SOD) are rare autosomal recessive conditions of sulfur-containing amino acid metabolism with overlapping clinical features and emerging therapies. The clinical phenotype is indistinguishable and they can only be differentiated biochemically. MOCS1, MOCS2, MOCS3, and GPRN genes contribute to the synthesis of molybdenum cofactor, and SUOX gene encodes sulfite oxidase. The aim of this study was to elucidate the clinical, radiological, biochemical and molecular findings in patients with SOD and MoCD. Methods Detailed clinical and radiological assessment of 9 cases referred for neonatal encephalopathy with hypotonia, microcephaly, and epilepsy led to a consideration of disorders of sulfur-containing amino acid metabolism. The diagnosis of six with MoCD and three with SOD was confirmed by biochemical tests, targeted sequencing, and whole exome sequencing where suspicion of disease was lower. Results Novel SUOX mutations were detected in 3 SOD cases and a novel MOCS2 mutation in 1 MoCD case. Most patients presented in the first 3 months of life with intractable tonic–clonic seizures, axial hypotonia, limb hypertonia, exaggerated startle response, feeding difficulties, and progressive cystic encephalomalacia on brain imaging. A single patient with MoCD had hypertrophic cardiomyopathy, hitherto unreported with these diseases. Interpretation Our results emphasize that intractable neonatal seizures, spasticity, and feeding difficulties can be important early signs for these disorders. Progressive microcephaly, intellectual disability and specific brain imaging findings in the first year were additional diagnostic aids. These clinical cues can be used to minimize delays in diagnosis, especially since promising treatments are emerging for MoCD type A.

IMPORTANCEThe study establishes the importance of genetic background for the expression of Down syndrome phenotype.OBJECTIVE To define the ocular manifestations of Down syndrome in infants and children in Cairo, Egypt, a historically isolated region, and compare them with systemic features and with findings in other geographic groups. DESIGN AND PARTICIPANTSWe prospectively studied the ocular status and systemic features of 90 infants and children with Down syndrome and monitored all patients for 3 years. The complete ophthalmic examinations were performed along with ultrasonography, if media opacities were evident. Thyroid and cardiac status were assessed. An extensive literature search for comparison was performed.SETTING Outpatient clinical genetics department at the National Research Centre in Cairo, Egypt. MAIN OUTCOMES AND MEASURESOcular and systemic manifestations of Down syndrome in infants and children in Cairo, and comparison of these features with patients with this anomaly from other geographic regions and ethnic populations.RESULTS Fifty-two infants or children (58%) had at least 1 abnormal ocular finding identified at the first visit. Significant refractive errors (in 37 [41%] patients) were the most common. Nasolacrimal duct obstruction, blepharoconjuctivitis, or conjunctivitis was found in 18 (20%), strabismus in 13 (14%), cataract in 5 (6%), nystagmus in 3 (3%), and optic nerve dysplasia in 2 (2%). Brushfield spots were not found. Additional ocular features developed over time. Thirty-six patients (40%) had congenital heart defects, and many (31 [86%]) had associated ocular disorders; a statistically significant correlation with myopia was established. Chromosomal translocations were high. The phenotype in Cairo was distinct.CONCLUSIONS AND RELEVANCE More than half of infants and children with Down syndrome in Cairo had ophthalmic abnormalities; myopia was correlated with congenital heart defects. Comparison of the specific ocular features in our population with those in previous worldwide studies shows differences that may be related to overexpression or polymorphisms of key, modifying genes or other mutations in this historically isolated region along the Nile River. Down syndrome is more common in the highly consanguineous and multiparous Middle Eastern populations, and our Cairo findings underscore regional differences.

Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1−/− mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy.

IntroductionTo assess the prevalence of metabolic risk indicators for the metabolic syndrome (MS) in a sample of obese Egyptian adolescents and to compare anthropometric and biochemical parameters in subjects with one or two parameters of the MS with those who meet MS criteria.Material and methodsA descriptive, cross-sectional study was conducted on 300 obese adolescents, with a mean age of 15.45 ±2.54 years. Variables examined included body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), systolic and diastolic blood pressure (BP), fasting blood glucose, cholesterol, triglycerides (TG), high-density lipoprotein (HDL), low-density lipoproteins (LDL), insulin and insulin resistance (IR) measured by Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). Receiver operating characteristic (ROC) curve analysis was used to determine the predictive powers of anthropometric parameters associated with increased risk for the MS.ResultsThe overall prevalence of the MS was 20%. Individuals meeting 3 or more MS criteria had significantly higher levels of BP, TG, glucose, insulin and HOMA-R and low HDL levels compared with those who had 1 or 2 MS criteria. Area under the curve (AUC) for identifying the MS risk factors was the highest for WHR, followed by WC and BMI in both genders (p < 0.001).ConclusionsThe most prevalent metabolic risk factors that compose the MS were arterial hypertension, low HDL and hypertriglyceridemia; BMI tended to be the weakest index for identifying MS risk factors, while WHR was the best predictive index in both genders.

Objectives:The aim of the present study was to investigate the serum paraoxonase 1 (PON1) concentration and oxidative stress markers and assess its relations with the biochemical parameters in obese adolescents.Materials and Methods:One hundred and fifty obese adolescents (range 16-18 years) and 150 healthy age- and sex-matched controls were enrolled in the study. The data were extracted from a project entitled “Obesity among Youth: Lifestyle and Genetic Factors” funded by the Science and Technology Development Fund, Egypt. Serum paraoxonase 1 (PON1), nitric oxide (NO), and malonaldehyde were measured. Anthropometry, fasting glucose, insulin concentrations, total cholesterol, high density lipoprotein–cholesterol, low density lipoprotein–cholesterol, triglycerides, systolic and diastolic blood pressure (BP) were measured. Insulin resistance was determined by Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Diagnostic accuracy of oxidative markers to identify dyslipidemia was calculated with ROC analysis.Results:The study showed that PON1 activity was significantly lower in obese adolescents than controls. Obese adolescents had significant lower NO level and significant increased MA values as compared to controls. PON1 was negatively correlated with MAD and body mass index in obese subjects. Obese adolescents showed dyslipidemia and increased blood pressure and HOMA-IR values. PON1 had high area under the curve in ROC analysis for identifying dyslipidemia in obese subjects.Conclusions:Our results indicate that obese subjects have increased oxidative stress and decreased PON1 activity. The lower paraoxonase level might contribute to the greater risk of dyslipidemia, insulin resistance, high blood pressure that are considered as important components in the pathogenesis of the metabolic syndrome in obese adolescents.

Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms.

Recent work demonstrated the presence of Helicobacter pylori (H. pylori) in the bile and gallbladder of more than 75 % of patients with gallbladder cancer and more than 50 % of patients with chronic cholecystitis. The aim of the work was to determine the prevalence of H. pylori in the gallbladder of patients operated on for chronic cholecystitis and relating their presence to the precancerous histological changes. In our study, fifty patients were operated on for chronic cholecystitis. The patients were subdivided into two groups (each includes 25 patients): H. pylori-positive group, who had H. pylori in their gallbladder mucosa detected by Giemsa stain, and H. pylori-negative group. The histological findings (mucosal erosions, atrophy, metaplasia, dysplasia, lymphoid infiltration, musculosa hypertrophy, and fibrosis) were compared between the two groups. Comparing the histological findings of the H. pylori-infected gallbladders with the non-infected ones, the gallbladders with mucosal hyperplasia, metaplasia/dysplasia, and lymphoid infiltration showed statistically significant differences, with a P value of 0.028, 0.049, and 0.022, respectively. On the other hand, no statistically significant differences were detected between the two groups in the degree of mucosal erosions (P = 0.299), atrophy, musculosa hypertrophy (P = 1.000), and fibrosis (P = 1.000). These results highlight the role of H. pylori infection in aggravating the mucosal lesions (mucosal hyperplasia, metaplasia, and lymphoid infiltration) of the gallbladder that is considered potentially precancerous.