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Introduction: One of the most significant current discussions in pediatrics is whether lumbar puncture (LP) should be performed in children with febrile seizure (FS) as in the past. Objectives: We compared the prevalence of meningitis among FS children before and after the pentavalent vaccine to determine the importance of the LP in these children. Methods: We performed a retrospective cross-sectional study on the prevalence and etiology of bacterial meningitis (BM) in 1314 children with FS before and after pentavalent vaccination. Results: We found that complex FS was more prevalent in patients aged under 12 months compared to other patients. The peak incidence of aseptic meningitis and BM was in the age group of 12- to 18- and 18- to 36-month-old, respectively (P value <0.001 and <0.05, respectively). Children with complex FS had a significantly higher rate of BM and a lower rate of seizure recurrence than those with simple FS (P value <0.05). There was a significant relationship between getting the pentavalent vaccine and reducing the prevalence of BM and Hib-induced BM, but no SP-induced BM (P value <0.05 and 0.05 and 0.104, respectively). Conclusion: This study offers some insights into the effectiveness of the pentavalent vaccine. In addition, the low prevalence of BM in vaccinated FS cases does not support strong recommendations for LP in FS children.
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We investigated the association of anticardiolipin antibodies (aCL) with epilepsy development and characteristics in children. This prospective case-control study included 40 epileptic children and 40 sex- and age-matched controls. Epileptic children had higher levels of aCL compared to healthy controls (5.66 ± 5.41 versus 2.37 ± 2.28; p value = 0.001). The novel finding of elevated levels of aCL predicted response to IVIg therapy (p value = 0.009). Patients with normal EEG had lower levels of aCL compared to those with EEG abnormal findings (p value = 0.015). Patients with the combined type of epilepsy had statistically significant higher levels of aCL compared to other types (p value = 0.046). Also, aCL levels were correlated with seizure frequency (p value = 0.019). These results declare the possible involvement of such antibodies in the onset or pathogenesis of epilepsy. Screening for aCL may help in the timely diagnosis of epilepsy and initiation of appropriate treatment.
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Background: The ATM gene encodes a multifunctional kinase involved in important cellular functions, such as checkpoint signaling and apoptosis, in response to DNA damage. Bi-allelic pathogenic variants in this gene cause Ataxia Telangiectasia (AT), while carriers of ATM pathogenic variants are at increased risk of cancer depending on the pathogenicity of the variant they carry. Identifying pathogenic variants can aid in the management of the disease in carriers. Methods: Whole-exome sequencing (WES) was performed on three unrelated patients from the Iranian-Azeri Turkish ethnic group referred to a genetic center for analysis. WES was also conducted on 400 individuals from the same ethnic group to determine the frequencies of all ATM variants. Blood samples were collected from the patients and their family members for DNA extraction, and PCR-Sanger sequencing was performed to confirm the WES results. Results: The first proband with AT disease had two novel compound heterozygote variants (c.2639-2A>T, c.8708delC) in the ATM gene revealed by WES analysis, which was potentially/likely pathogenic. The second proband with bi-lateral breast cancer had a homozygous pathogenic variant (c.6067G>A) in the ATM gene identified by WES analysis. The third case with a family history of cancer had a heterozygous synonymous pathogenic variant (c.7788G>A) in the ATM gene found by WES analysis. Sanger sequencing confirmed the WES results, and bioinformatics analysis of the mutated ATM RNA and protein structure added evidence for the potential pathogenicity of the novel variants. WES analysis of the cohort revealed 38 different variants, including a variant (rs1800057, ATM:c.3161C>G, p.P1054R) associated with prostate cancer that had a higher frequency in our cohort. Conclusion: Genetic analysis of three unrelated families with ATM-related disorders discovered two novel pathogenic variants. A homozygous missense pathogenic variant was identified in a woman with bi-lateral breast cancer, and a synonymous but pathogenic variant was found in a family with a history of different cancers.
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Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder featuring impairment in verbal and non-verbal interactions, defects in social interactions, stereotypic behaviors as well as restricted interests. In recent times, the incidence of ASD is growing at a rapid pace. In spite of great endeavors devoted to explaining ASD pathophysiology, its precise etiology remains unresolved. ASD pathogenesis is related to different phenomena associated with the immune system; however, the mechanisms behind these immune phenomena as well as the potential contributing genes remain unclear. In the current work, we used a bioinformatics approach to describe the role of long non-coding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) in the peripheral blood (PB) samples to figure out the molecular regulatory procedures involved in ASD better. The Gene Expression Omnibus database was used to obtain the PB microarray dataset (GSE89594) from the subjects suffering from ASD and control subjects, containing the data related to both mRNAs and lncRNAs. The list of immune-related genes was obtained from the ImmPort database. In order to determine the immune-related differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs), the limma package of R software was used. A protein-protein interaction network was developed for the immune-related DEmRNAs. By employing the Human MicroRNA Disease Database, DIANA-LncBase, and DIANA-TarBase databases, the RNA interaction pairs were determined. We used the Pearson correlation coefficient to discover the positive correlations between DElncRNAs and DEmRNAs within the ceRNA network. Finally, the lncRNA-associated ceRNA network was created based on DElncRNA-miRNA-DEmRNA interactions and co-expression interactions. In addition, the KEGG enrichment analysis was conducted for immune-related DEmRNAs found within the constructed network. This work found four potential DElncRNA-miRNA-DEmRNA axes in ASD pathogenesis, including, LINC00472/hsa-miR-221-3p/PTPN11, ANP32A-IT1/hsa-miR-182-5p/S100A2, LINC00472/hsa-miR-132-3p/S100A2, and RBM26-AS1/hsa-miR-182-5p/S100A2. According to pathway enrichment analysis, the immune-related DEmRNAs were enriched in the "JAK-STAT signaling pathway" and "Adipocytokine signaling pathway." An understanding of regulatory mechanisms of ASD-related immune genes would provide novel insights into the molecular mechanisms behind ASD pathogenesis.
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OBJECTIVE: Subependymal Giant Cell Astrocytomas (SEGAs) are slow-growing glioneuronal tumors typically found around the ventricles of the brain, particularly near the foramen of Monro in 15%-20% of patients with tuberous sclerosis complex (TSC). Surgical resection is the standard treatment for these symptomatic tumors. The mTOR inhibitor everolimus can be regarded as an alternative treatment for SEGAs due to the complications of surgery. The present study primarily aimed to specify the effect of everolimus on SEGA volume change before and after treatment. The secondary objective was to determine the effect of this drug on renal angiomyolipoma (AML), skin lesions, and seizures in TSC patients. MATERIALS & METHODS: This pre- and post-treatment clinical trial was performed on 14 children (eight females and six males with a mean age of 10 years) previously diagnosed with TSC based on the diagnostic criteria. The subjects received oral everolimus at a dose of 3 mg/m2 for at least six months. RESULTS: Half of the patients had more than 30% of volume loss in SEGA, and in 28.5% of them, a ≥ 50% reduction in SEGA volume was observed (P=0.01). Moreover, 92.9% of the patients had a ≥ 50% decrease in the frequency of seizures (P=0.000). The response rate in AML and skin lesions was 14.2% and 50%, respectively. CONCLUSION: Everolimus significantly reduced the seizure frequency and SEGA volume in the subjects; hence, it can be used as a potential alternative treatment for symptomatic SEGA in TSC patients.
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Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder that involves social interaction defects, impairment of non-verbal and verbal interactions, and limited interests along with stereotypic activities. Its incidence has been increasing rapidly in recent decades. Despite numerous attempts to understand the pathophysiology of ASD, its exact etiology is still unclear. Recent data shows the role of accurate myelination and translational regulation in ASD's pathogenesis. In this study, we assessed Ermin (ERMN) and Listerin E3 Ubiquitin Protein Ligase 1 (LTN1) genes expression in Iranian ASD patients and age- and gender-matched healthy subjects' peripheral blood using quantitative real-time PCR to recognize any probable dysregulation in the expression of these genes and propose this disorder's mechanisms. Analysis of the expression demonstrated a significant ERMN downregulation in total ASD patients compared to the healthy individuals (posterior beta = -0.794, adjusted P-value = 0.025). LTN1 expression was suggestively higher in ASD patients in comparison with the corresponding control individuals. Considering the gender of study participants, the analysis showed that the mentioned genes' different expression levels were significant only in male subjects. Besides, a significant correlation was found between expression of the mentioned genes (r = -0.49, P < 0.0001). The present study provides further supports for the contribution of ERMN and LTN1 in ASD's pathogenesis.
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Dietary therapy has an important role in the therapeutic process in children suffering refractory epilepsy. There are two kinds of dietary therapy which are the most common in children with refractory epilepsy: The classic ketogenic diet (KD) and the modified Atkins diet (MAD). The purpose of the present study was to compare the efficacy, tolerability, and compliance of these two dietary therapies in the children who have refractory epilepsy during 6 months of treatment. From March 2017 to November 2018, 45 children aged 2-15 years who had refractory epilepsy were randomly allocated in KD or MAD group. The intervention period was 6 months in both groups. The frequencies of seizures were determined from parental reports and were compared between the groups. The patients with upper than 50% reduction in seizure frequency were deemed as responders to the diets. Twenty-four patients were assigned to the KD and 11 patients to the MAD. Overall, 45.8% of children treated with the KD and 45.5% of children treated with MAD had over than 50% response to the diet therapies. The difference was not statistically significant (P = 0.437). The MAD was more advantageous regarding better tolerability and fewer side effects. There is not much difference regarding the efficacy between the MAD and classic KD. The MAD with fewer side effects may be more suitable as the first line of dietary therapy in children with refractory epilepsy.
Subject(s)
Diet, High-Protein Low-Carbohydrate/methods , Diet, Ketogenic/methods , Drug Resistant Epilepsy/diet therapy , Drug Resistant Epilepsy/diagnosis , Adolescent , Child , Child, Preschool , Diet, High-Protein Low-Carbohydrate/trends , Diet, Ketogenic/trends , Female , Follow-Up Studies , Humans , Male , Treatment OutcomeABSTRACT
Pompe disease (PD) is a rare autosomal recessive multi-systemic lysosomal storage disorder, caused by mutations in the acid alpha-glucosidase (GAA) gene located on 17q25.2-q25.3. It is one of about 50 rare genetic diseases categorized as lysosomal storage disorders. This disease is characterized by a range of different symptoms related to acid alpha-glucosidase deficiency. Mutation recognition in the GAA gene can be very significant for purposes such as therapeutic interference, early diagnosis and genotype-phenotype relationship. In the current study, peripheral blood samples were gathered from patients with PD and healthy members of three families. Enzymatic activity of GAA was checked. Then, mutation detection was performed by polymerase chain reaction followed by direct sequencing of all exons in samples with decreased enzyme activity. The identified mutations were investigated using bioinformatics tools to predict possible effects on the protein product and also to compare the mutated sequence with near species. Three novel mutations (c.1966-1968delGAG, c.2011-2012delAT and c.1475-1481dupACCCCAC) were identified in the GAA gene. Assessment of the effects of these mutations on protein structure and function showed the possibility of harmful effects and their significant alterations in the protein structure. The three novel GAA gene mutations detected in this study expand the information about the molecular genetics of PD and can be used to helpdiagnosis and genetic counseling of affected families.
Subject(s)
Glycogen Storage Disease Type II/genetics , Mutation , alpha-Glucosidases/genetics , Adolescent , Child , Child, Preschool , DNA Mutational Analysis , Female , Genetic Predisposition to Disease , Glycogen/metabolism , Glycogen Storage Disease Type II/metabolism , Humans , Infant , Male , Turkey , alpha-Glucosidases/metabolismABSTRACT
Introduction: Valproic acid (VPA) is an antiepileptic drug used to treat epilepsy and bipolar disorder. Adverse effects of VPA were studied in many reports, however, a dose-response relationship between VPA and its metabolites in epilepsy patients are extremely limited. In this paper, a high efficient method was developed for the preconcentration and determination of VPA and its main metabolite in plasma. Methods: For the extraction and preconcentration of the selected analytes, a volume of an extractant was placed at the bottom of the microtube containing pretreated plasma. The mixture was repeatedly withdrawn from the microtube and pushed-out into it using a 1.0-mL glass syringe and resulted in a cloudy mixture. For further turbidity, the mixture was shaken on a vortex agitator. This procedure was used to analyze the plasma samples of patients with epilepsy (n = 70). Results: The results revealed that in most patients with a low level of VPA relative to its expected level, 3-heptanone concentrations were high. The limits of quantification of 3-heptanone and VPA were 0.04 mg L-1 and 0.2 mg L-1, respectively. A suitable precision at a concentration of 2 mg L-1 for each analyte was obtained (relative standard deviation ≤ 9%). Conclusion: The obtained results indicated that this procedure is easy, sensitive, and reliable, and can be used for the analysis of the selected analytes in the plasma samples of patients with epilepsy.
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Neuronal ceroid lipofuscinoses (NCLs) are a group of neurodegenerative disorders caused by mutations in fourteen distinct ceroid lipofuscinoses, neuronal (CLN) genes described with various severe symptoms such as seizures, visual failure, motor decline, and progressive cognitive deterioration. The current research represents novel CLN5 (c.741G > A) and CLN8 (c.565delT) mutations in two different Iranian families with late-infantile NCL (LINCL) and their relatives by using whole-exome sequencing (WES). The first family had a 10-year-old male with consanguineous parents and severe NCL symptoms, including motor clumsiness, telangiectasia, and cerebellar atrophy. The second family with a child who suffered from nystagmus rotation, motor difficulties, and seizure was a 5-year-old male with consanguineous parent. WES of probands 1 and 2 revealed homozygotic mutations in exon 4 of CLN5 (c.741G > A, p.W247X) and deletion in exon 3 (c.565delT, p.F189fs) of CLN8, respectively. Both patients' parents were heterozygous for these alterations. In concordance with previous studies, our results indicate that pathogenic mutations in CLN genes, especially CLN5 and 8, are a main cause of LINCL; these results also suggest that LINCL is not a regionally or nationally dependent disorder and can occur in any ethnic group despite the fact that some populations may be more at risk. Consequently, CLN gene screening for patients with typical signs of LINCL is recommended.
Subject(s)
Loss of Function Mutation , Lysosomal Membrane Proteins/genetics , Lysosomes/physiology , Membrane Proteins/genetics , Neuronal Ceroid-Lipofuscinoses/genetics , Child , Child, Preschool , Codon, Nonsense , Consanguinity , Exons/genetics , Female , Genotype , Humans , Iran , Lysosomal Membrane Proteins/physiology , Magnetic Resonance Imaging , Male , Membrane Proteins/physiology , Models, Molecular , Neuroimaging , Neuronal Ceroid-Lipofuscinoses/diagnostic imaging , Neuronal Ceroid-Lipofuscinoses/pathology , Pedigree , Protein Processing, Post-Translational , Sequence Deletion , Exome SequencingABSTRACT
OBJECTIVE: Poor bone health with related morbidity is a major problem with Duchene Muscular Dystrophy (DMD). Decreased mobility and long-term corticosteroid therapy are involved in poor bone health in DMD. We investigated bone mineral density and bone metabolism in 30 steroid treated DMD patients and also compared mentioned factors between ambulated and non-ambulated patients. MATERIALS & METHODS: In this cross-sectional study, 30 boys (21 patients ambulate and 9 non-ambulate) with documented DMD, according to genetic analysis, were enrolled in 2015. Demographic characteristics, neurologic exam findings, muscle function score, corticosteroid dose and duration and food frequency questionnaire were recorded. Bone mineral density was measured with dual- energy X-ray absorptiometry (DEXA) on lumbar spine and left proximal femur. Serum 25-hydroxyvitamin D, calcium, phosphorus and parathyroid hormone (PTH) levels were measured. RESULTS: Osteoporosis was found in 86.7% patients. Mean bone density in the lumbar spine was -1.5±0.24 and -1.4±0.27 in ambulates and non-ambulates respectively (P=0.7). Mean bone density at proximal femur was -3.4±0.2 in ambulates and -3.4±0.3 in non-ambulates (P =0.48). Intra-groups statistical analysis showed significant difference between bone mineral density at lumbar spine and proximal femur in both mentioned groups (P<0.05). Vitamin D deficiency was detected in 13 patients (43.3%) and its serum level was significantly lower in non-ambulates compared with ambulates. CONCLUSION: Considering high prevalence of vitamin D deficiency and osteoporosis in DMD patients, it seems vitamin D supplementation can improve vitamin D status and osteoporosis in these patients, especially in non-ambulates.
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OBJECTIVE: Duchene and Becker Muscular Dystrophy (DMD/ BMD) are x-linked disorders that both are the result of heterogeneous mutations in the dystrophin gene. The frequency and distribution of dystrophin gene deletions in DMD/ BMD patients show different patterns among different populations. This study investigates the deletion rate, type, and distribution of this gene in the Azeri Turk population of North West Iran. MATERIALS &METHODS: In this study, 110 patients with DMD/ BMD were studied for intragenic deletions in 24 exons and promoter regions of dystrophin genes by using multiplex PCR. RESULTS: Deletions were detected in 63 (57.3%) patients, and around 83% localized in the mid-distal hotspot of the gene (on exons 44-52), 21 cases (33.3 %) with single-exon deletions, and 42 cases (66.6%) with multi-exonic deletions. The most frequent deleted exons were exon 50 (15 %) and exon 49 (14%). No deletion was detected in exon 3. CONCLUSION: This study suggests that the frequency and pattern of dystrophin gene deletions in DMD/ BMD in the Azeri Turk population of North West Iran occur in the same pattern when compared with other ethnic groups.
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BACKGROUND: Psychosocial problems seem to be common in epilepsy, and they could negatively affect the social affairs and networking of adolescents with epilepsy. They could cause decreased self-esteem and social performance, leading to isolation and civil discrimination. This study was performed to assess the quality of life (QOL) of a group of adolescents with epilepsy in Iran. METHODS: An analytic cross-sectional study was performed in 197 young Iranian adolescents with epilepsy. To measure the QOL of these cases, the Persian version of the QOL in Epilepsy Inventory for Adolescents 48 (QOLIE-AD-48) scale was used. RESULTS: The mean total score of the scale was 61.5±10.4. The highest mean was in the school behavior domain (83.85±12.27), while the lowest mean was in the domain of attitudes toward epilepsy (22.45±15.78). There was a significant correlation between QOL and age, number of drugs taken, and frequency of seizures per year. Sixty-six percent of the adolescents with epilepsy had never talked to their friends or teachers about their disease. CONCLUSION: This study revealed an unsatisfactory state of the QOL of adolescents with epilepsy in our population in comparison with other studies. This indicates the need for greater concern about the psychological status and risk factors for the QOL of adolescents with epilepsy in Iran.
Subject(s)
Epilepsy/psychology , Quality of Life/psychology , Self Concept , Adolescent , Child , Cross-Sectional Studies , Female , Health Status , Health Surveys , Humans , Iran , Male , Mental Health , Surveys and QuestionnairesABSTRACT
Dermal melanocytosis (DM) is described as the presence of ectopic melanocytes in the dermis and could be a normal cutaneous finding. However, diffuse DM or extensive Mongolian spots must be considered as an early sign of neurometabolic diseases, in particular lysosomal storage disorders. The presence of extensive DM should alert the physician to the presence of such disorders, making early diagnosis possible. We describe for the first time the presence of DM in two patients with Sandhoff disease and mucopolysaccharidosis VI.
Subject(s)
Melanocytes/pathology , Mongolian Spot/diagnosis , Mucopolysaccharidosis VI/diagnosis , Sandhoff Disease/diagnosis , Skin Neoplasms/diagnosis , Child, Preschool , Female , Humans , Infant , Prognosis , Risk Assessment , Sampling StudiesABSTRACT
OBJECTIVE: Precocious puberty is of concern because of the underlying disorders, the short adult stature, and the psychosocial difficulties. This study was carried out in order to evaluate the characteristics of children referred to pediatric endocrinology clinic with diagnosis of precocious puberty. METHODS: In a cross-sectional study between February 2007 and September 2009, all of the children referred to pediatric endocrinology clinic in North-West Iran with diagnosis of precocious puberty were recruited. FINDINGS: Data of 106 girls (82.2%) and 23 boys (17.8%) were analyzed. Mean age of the patients at the time of referral was 6.6±2.8 years (ranging 0.3-14 yr), which was 7±3.9 (ranging 0.3-14 yr) for boys and 6.6±2.5 (ranging 0.8-12 yr) for girls (P=0.6). Out of 129 subjects, 56(43.4%) had precocious puberty, 71.4% (35 cases) of them were due to central precocious puberty and 28.6% (16 cases) were pseudo-precocious puberty. 73 out of 129 subjects (56.6%) were due to normal variants of puberty, normal puberty, and no puberty. 87.5% of subjects with central precocious puberty were idiopathic. CONCLUSION: Most of children referred with diagnosis of precocious puberty have benign normal variants. Most of cases with precocious puberty are affected with central precocious puberty, especially with idiopathic form of it.
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INTRODUCTION: An outcome-based education approach has been proposed to develop more effective continuing medical education (CME) programs. We have used this approach in developing an outcome-based educational intervention for general physicians working in primary care (GPs) and evaluated its effectiveness compared with a concurrent CME program in the field of rational prescribing. METHODS: A cluster randomized controlled design was used. All 159 GPs working in 6 cities, in 2 regions in East Azerbaijan province in Iran, were invited to participate. The cities were matched and randomly divided into an intervention arm, for an outcome-based education on rational prescribing, and a control arm for a traditional CME program on the same topic. GPs' prescribing behavior was assessed 9 months before, and 3 months after the CME programs. RESULTS: In total, 112 GPs participated. The GPs in the intervention arm significantly reduced the total number of prescribed drugs and the number of injections per prescription. The GPs in the intervention arm also increased their compliance with specific requirements for a correct prescription, such as explanation of specific time and manner of intake and precautions necessary when using drugs, with significant intervention effects of 13, 36, and 42 percentage units, respectively. Compared with the control arm, there was no significant improvement when prescribing antibiotics and anti-inflammatory agents. DISCUSSION: Rational prescribing improved in some of the important outcome-based indicators, but several indicators were still suboptimal. The introduction of an outcome-based approach in CME seems promising when creating programs to improve GPs' prescribing behavior.