Search

Children with autism spectrum disorder (ASD) are usually unable to express abdominal discomfort properly, and thus gastrointestinal symptoms (GIS) are sometimes shadowed by aggression, which is sometimes misunderstood as a behavioral characteristic of ASD. Several studies have reported interesting correlations between the severity of behavioral and gastrointestinal symptoms in ASD children. The present study aimed to investigate the potential effects of probiotics as an adjuvant therapy to modulate the clinical status of ASD children. This study included 40 children with ASD aged 2-5 years. The feeding product was prepared from whey powder (without casein) and some minced cooked yellow vegetables in adequate ratios fortified with the studied probiotic strains (Bifidobacterium spp. and Lactobacillus spp.). Bifidobacterium strains were assessed from stool samples of children with ASD. Bifidobacterium strains were analyzed in the stools of ASD children. Recruited ASD patients received 10 g of the nutritional supplement once a day for 3 months. Childhood Autism Rating Scale (CARS) and Autism Diagnostic Interview-Revised (ADIR) were reevaluated clinically. Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III Version was used for all children with ASD before and after. There is a significant increase in the colony counts of both Bifidobacterium spp. and Lactobacillus spp., which present in the stool of ASD children after probiotic supplementation for 3 months. It was highly significant in the case of Bifidobacterium spp. (p value 0.000) and a significant increase in Lactobacillus spp. (p value 0.015). The present study showed reduced anxiety and observation of deep sleep for children with ASD (80%) after taking the supplementation. This indicates that probiotics may have a potential effect in reducing symptoms and severity of ASD and in correcting dysbiosis.

Obesity is more prevalent among people with Down Syndrome (DS) compared to general population. In this pilot study, we investigated the effect of cystathionine beta-synthase (CBS) overdosage on the regulation of transsulfuration pathway and the obesity phenotype in fifty adolescents (25 obese/overweight and 25 lean) with trisomy 21.The transcriptional levels ofBoth DS groups had comparable levels ofOur data suggests that the high concentrations of CBS enzyme together with cysteine modulate the DS obesity presumably through increased hydrogen sulfide production which has recently showed anti-adiposity effects.

The aim of the current study is the development of a vitamin D3 (VD3)-loaded nanoemulsion (NE) formulation to improve VD3 oral bioavailability for management of vitamin D inadequacy in autistic children. Eight NE formulations were prepared by high-speed homogenization followed by ultrasonication. Four vegetable oils were employed along with two concentrations of Span 20 as the emulsifier. Glycerol, fructose, and mango flavor were included as viscosity modifier, sweetening, and flavoring agents, respectively. The prepared VD3-loaded NE formulations exhibited high drug content (> 98%), droplet size (DS) ranging from 61.15 to 129.8 nm with narrow size distribution, zeta potential values between − 9.83 and − 19.22 mV, and acceptable pH values (4.59–5.89). Storage stability showed that NE formulations underwent coalescence and phase separation during 6 months at room temperature, whereas at refrigerated conditions, formulations showed slight creaming. The optimum formulation (VD3-NE6) revealed a non-significant DS growth at refrigerated conditions and spherical morphology under transmission electron microscopy. VD3-NE6 did not produce any toxic effects to rats treated orally for 3 months, where normal blood picture and kidney and liver functions were observed compared to control rats. Also, serum calcium, oxidative stress, and apoptosis biomarkers remained within normal levels, indicating the safety of the optimum formulation. Furthermore, evaluation of VD3-NE6 oral bioavailability depicted a significant increase in AUC0–72 and Cmax with decreased Tmax compared to plain VD3. The optimum formulation demonstrated improved stability, safety, and oral bioavailability indicating the potential for successful management of vitamin D deficiency in autistic children.

Autism spectrum disorder (ASD) and epilepsy run hand-to-hand in their pathophysiology. Epilepsy is not an uncommon finding in patients with ASD. The aim of the present study was to identify the metabolic abnormalities of BCAAs (leucine, isoleucine, and valine) in children with ASD with and without seizures in comparison with neurotypical controls. Also, this study aimed to investigate the presence of epileptiform discharges on electroencephalography (EEG) in ASD patients and to describe the types and frequency of seizures observed. The study included 90 children aged 2-7 years, 30 of whom were diagnosed with both ASD and epilepsy. The other 30 children were diagnosed as ASD without epilepsy, and a comparable 30 normally developed children served as a control group. The groups were matched by age and gender. All patients were referred to the Autism Disorders Clinic for interviews and examinations. The Childhood Autism Rating Scale (CARS) was applied to all study participants to assess the degree of autism. The present study results show that all types of seizures may be identified in ASD children. The median serum levels of BCAAs were lower in ASD children with and without epilepsy than in neurotypical controls. This opens the door for discussion about new etiologies and better categorizations of ASD based on genotype and genetic abnormalities detected. More studies with larger samples are needed to understand ASD better and to more reliable evaluate the association between ASD, EEG changes, seizures, and BCAAs.

According to the United States Centers for Disease Control and Prevention (CDC), as of July 11, 2016, the reported average incidence of children diagnosed with an autism spectrum disorder (ASD) was 1 in 68 (1.46%) among 8-year-old children born in 2004 and living within the 11 monitoring sites' surveillance areas in the United States of America (USA) in 2012. ASD is a multifaceted neurodevelopmental disorder that is also considered a hidden disability, as, for the most part; there are no apparent morphological differences between children with ASD and typically developing children. ASD is diagnosed based upon a triad of features including impairment in socialization, impairment in language, and repetitive and stereotypic behaviors. The increasing incidence of ASD in the pediatric population and the lack of successful curative therapies make ASD one of the most challenging disorders for medicine. ASD neurobiology is thought to be associated with oxidative stress, as shown by increased levels of reactive oxygen species and increased lipid peroxidation, as well as an increase in other indicators of oxidative stress. Children with ASD diagnosis are considered more vulnerable to oxidative stress because of their imbalance in intracellular and extracellular glutathione levels and decreased glutathione reserve capacity. Several studies have suggested that the redox imbalance and oxidative stress are integral parts of ASD pathophysiology. As such, early assessment and treatment of antioxidant status may result in a better prognosis as it could decrease the oxidative stress in the brain before it can induce more irreversible brain damage. In this review, many aspects of the role of oxidative stress in ASD are discussed, taking into account that the process of oxidative stress may be a target for therapeutic interventions.

Background Down syndrome (DS) is characterized by variable degrees of intellectual disability (ID). The coronavirus disease-2019 (COVID-19) lockdown prevented children with DS from reaching their rehabilitation facilities. This could have led to deterioration of their abilities and mental health hazards. The aim of this cohort study was to investigate frequency of COVID-19, the influence of COVID-19 pandemic on health, and some abilities of children with DS, and to explore factors that could have governed receiving home-based training during the lockdown. A survey of 150 individuals with Down syndrome was answered by their caregivers. Additionally, 135 participants were subjected to assessment of cognitive, language, and motor abilities using Portage program. They were divided into 2 groups: group I who received online therapy sessions during the lockdown and group II who did not receive sessions. Logistic regression was used to determine the factors which influenced getting home-based training. Results The percentage of COVID-19 cases was 3.3%. All evaluated abilities were reduced despite receiving online sessions particularly language performance (P Conclusion COVID-19 pandemic had a negative impact on the abilities of DS children even those who got rehabilitation sessions. Their dependence on social interaction could have limited the benefit of virtual sessions. Factors that influence a parent’s decision to get home-based training should be monitored and targeted in order to overcome obstacles or concepts that may prevent families from enduring home-based intervention.

Background Autism spectrum disorder is a condition related to brain development that affects a person’s perception and socialization, resulting in problems in social interaction and communication. It has no single known cause, yet several different genes appear to be involved in autism. As a genetically complex disease, dysregulation of miRNA expression and miRNA–mRNA interactions might be a feature of autism spectrum disorder. The aim of the current study was to investigate the expression profile of circulating miRNA-128, miRNA-7 and SHANK gene family in ASD patients and to assess the possible influence of miRNA-128 and miRNA-7 on SHANK genes, which might provide an insight into the pathogenic mechanisms of ASD and introduce noninvasive molecular biomarkers for the disease diagnosis and prognosis. Quantitative real-time PCR technique was employed to determine expression levels of miRNA-128, miRNA-7 and SHANK gene family in blood samples of 40 autistic cases along with 30 age- and sex-matched normal volunteer subjects. Results Our study revealed a statistical significant upregulation of miRNA-128 expression levels in ASD cases compared to controls (p value SHANK-3 expression was encountered on comparing cases to controls (p value Conclusions MiRNA-128 and SHANK-3 gene are emerging players in the field of ASD. They are promising candidates as noninvasive biomarkers in autism. Future studies are needed to emphasize their pivotal role.

Hyperserotonemia and brain-specific autoantibodies are detected in some autistic children. Nerve growth factor (NGF) stimulates the proliferation of B lymphocytes with production of antibodies and also increases mast cell serotonin release. This work was the first to investigate the relationship between plasma NGF and both hyperserotonemia and the frequency of serum anti-myelin basic protein (anti-MBP) auto-antibodies in 22 autistic children aged between 4 and 12 years and 22 healthy-matched controls. Levels of NGF, serotonin and anti-MBP were significantly higher in autistic children than healthy control children (P 0.001). There was a significant positive correlation between NGF and serotonin levels in autistic patients (P 0.01). In contrast, there was a non-significant correlation between NGF and anti-MBP levels (P 0.05). In conclusions, serum NGF levels were elevated and significantly correlated to hyperserotonemia found in many autistic children.

AIM: The aim of this research was to establish the perturbation of reliable biomarkers implicated in the pathophysiology of autism to help in the early diagnosis and to be as targets in the treatment of autism spectrum disorders (ASDs) in children and to spotlight into the complex crosstalk between these biomarkers. PATIENS AND METHODS: This study included 90 autistic children aged from 2 to 7 years old, who were classified into two groups, the atypical autism of 30 children and the childhood autism. The childhood autism group was further divided into mild-moderate autism group and severe autism group each of 30 children. The control group included 30 matched healthy children. All the participants were subjected to full psychiatric examinations, psychological investigations, and biochemical measurements, including gamma-aminobutaric acid (GABA), serotonin, dopamine (DA) in plasma, and brain-derived neurotrophic factor (BDNF) in serum. RESULTS: The autistic groups showed a highly significant increase in GABA, serotonin, DA, and BDNF levels compared to the control. Of note, the levels of GABA, DA, and BDNF were significantly increased with the increased disease severity. Furthermore, a significant positive correlation between BDNF levels and both GABA and DA levels in the childhood autism group has been recorded. CONCLUSION: The present clinical setting provides new insight into the fundamental role of BDNF in the brain of autistic children as any alterations of its level due to GABA increment cause change in serotonin and DA levels which have empirical evidence in the pathophysiology of ASD. The results received in this research, create a fertile base for the setup of particular targets in the intervention of this ailment.

There is an emerging body of evidence associating children having autism spectrum disorder (ASD) with gastrointestinal (GI) symptoms, such as abdominal pain, chronic diarrhea, constipation, vomiting, gastroesophageal reflux, intestinal infections, and increased intestinal permeability. Moreover, in many studies, large differences in the composition of intestinal microbiota and metabolic products between ASD patients and controls were reported. Deepening the role and the biology of the gut microbiome may be fundamental to elucidate the onset of GI symptoms in ASD individuals and their etiopathogenetic causes. The gut-brain axis may affect brain development and behaviors through the neuroendocrine, neuroimmune, and autonomic nervous systems.

Autism’s etiology is heterogeneous. It derives generically from a complex of interactions between genetic, epigenetic and environmental factors. Chromosomal rearrangements at almost all chromosomes have been reported among individuals with autism spectrum disorders (ASD). In this report, we represent three autistic patients with chromosomal abnormalities at 10q and 22q with an interesting case of 10q duplication rather than deletion. This report explores the contribution of the affected genomic regions to ASD. It may contribute to the field of research categorizing candidate loci for ASD, which would be useful in genotype– phenotype analyses for ASD.

Objective: To spot the frontal theta/beta ratio alterations during Tests of Variance of Attention (TOVA) in Egyptian attention deficit hyperactivity disorder (ADHD) children. Methods: This is a cross sectional study performed in Clinical Neurophysiology Unit, Cairo University, Egypt. It included 2 groups, each of 52 children (one of them with ADHD and the other were normal control). EEG was recorded for every subject during normal relaxing circumstance with eyes opened as well as during TOVA. Results: Comparing both groups revealed statistically significant difference in the theta/beta ratio in both state (normal relaxing with eyes opened and during TOVA), also we found that the theta/beta ratio decreased in normal group (during concentration) while in the ADHD group it increased with a specific pattern. Conclusion: The theta/beta ratio can be of value in helping for differential diagnosis in patients presenting with mild ADHD.

As a major neurodevelopmental disorder, Autism Spectrum Disorder (ASD) encompasses deficits in communication and repetitive and restricted interests or behaviors in childhood and adolescence. Its etiology may come from either a genetic, epigenetic, neurological, hormonal, or an environmental cause, generating pathways that often altogether play a synergistic role in the development of ASD pathogenesis. Furthermore, the metabolic origin of ASD should be important as well. A balanced diet consisting of the essential and special nutrients, alongside the recommended caloric intake, is highly recommended to promote growth and development that withstand the physiologic and behavioral challenges experienced by ASD children. In this review paper, we evaluated many studies that show a relationship between ASD and diet to develop a better understanding of the specific effects of the overall diet and the individual nutrients required for this population. This review will add a comprehensive update of knowledge in the field and shed light on the possible nutritional deficiencies, metabolic impairments (particularly in the gut microbiome), and malnutrition in individuals with ASD, which should be recognized in order to maintain the improved socio-behavioral habit and physical health.

Background and objective: Overweight and obesity are thought to be associated with increased risk of chronic disease in the Middle East. The present study aimed to determine the association between dietary habits and the incidence of overweight and obesity in urban adult population in the central part of Iran after a 10-year follow-up. Methods: This cohort study was initiated with 2000 participation aged 20e74 years from Yazd city in Iran based on Yazd Healthy Heart Project (YHHP). The participants without overweight and obesity at the baseline of the study were followed up to 10 years. Demographic data, anthropometric measurements, behavioral and metabolic risk factors of cardiovascular diseases and dietary habits were assessed at baseline and phase II. Results: After a 10-year follow up, 516 non-overweight and 1068 non-obese participants were included for the final analysis. Once adjustments were made for all potential confounders including age, sex, smoking, economic status, physical activity and education, it was identified that lack of weight control increased the risk of obesity (hazard ratio; 95% CI) in total population (1.9; 1.06, 3.4), as well as the risk of overweight (2.39; 1.07, 5.27) and obesity (2.65; 1.13, 6.25) in men. Moreover, consumption of mayonnaise increased the 10-year risk of overweight in women (6.09; 1.2, 30.99). Conclusions: As revealed by the present study, unhealthy dietary habits can increase the incidence of overweight and obesity in central part of Iran. Therefore, changing the lifestyle appears to be urgent in reducing the risk of overweight and obesity.

Current research has shown that gut microbiota may play a fundamental role in neurological activity, behavior, mood, cognition, and possibly for the onset as well as the severity of autism spectrum disorder (ASD). Previous studies emphasized the possible correlation between Clostridium spp., gut colonization, and possible development or exacerbating of ASD in affected children. The aim of the present study was to investigate how Clostridia gut colonization can have an impact on the neurological outcome and anthropometric values in ASD children. The present study included 60 children (30 ASD and 30 neurotypical controls) of both sexes aged from 2 to 8 years. Children with ASD were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), Autism Diagnostic Interview-Revised (ADI-R), as well as the Childhood Autism Rating Scale (CARS). Quantitative real-time polymerase chain reaction (real-time PCR) was used to determine Clostridium presence in the stools of the enrolled subjects. The number of Clostridium spp. (Clostridium paraputri, Clostridium bolteae, and Clostridium perfringens) found in the stools of ASD children was greater than neurotypical children. Children with ASD had two types of Clostridium (Clostridium diffiicile and Clostridium clostridiioforme) not found in neurotypical children, whereas neurotypical children yielded only one species (Clostridium tertium) not found in the ASD children. The present study emphasizes the potential correlation between gut colonization of Clostridia and the probability of developing or exacerbating ASD among Egyptian children. If Clostridium bacteria play a potential role in the etiology of ASD, this may open the possibility for effective treatment of these patients.

Autism spectrum disorder (ASD) is classified as a neurodevelopmental disorder characterized by reduced social communication as well as repetitive behaviors. Many studies have proved that defective synapses in ASD influence how neurons in the brain connect and communicate with each other. Synaptopathies arise from alterations that affecting the integrity and/or functionality of synapses and can contribute to synaptic pathologies. This study investigated the GABA levels in plasma being an inhibitory neurotransmitter, caspase 3 and 9 as pro-apoptotic proteins in 20 ASD children and 20 neurotypical controls using the ELISA technique. Analysis of receiver-operating characteristic (ROC) of the data that was obtained to evaluate the diagnostic value of the aforementioned evaluated biomarkers. Pearson's correlations and multiple regressions between the measured variables were also done. While GABA level was reduced in ASD patients, levels of caspases 3 and 9 were significantly higher when compared to neurotypical control participants. ROC and predictiveness curves showed that caspases 3, caspases 9, and GABA might be utilized as predictive markers in autism diagnosis. The present study indicates that the presence of GABAergic dysfunction promotes apoptosis in Egyptian ASD children. The obtained GABA synaptopathies and their connection with apoptosis can both relate to neuronal excitation, and imbalance of the inhibition system, which can be used as reliable predictive biomarkers for ASD.

The present research was carried out to elucidate the role of zinc (Zn) supplementation on the plasma concentration and gene expression, as well as the effects on cognitive-motor performance, in a cohort of children with autism spectrum disorder (ASD). The study was performed on a cohort of 30 pediatric subjects with ASD, encompassing an age range of 3–8 years. The impact of Zn supplementation was investigated in 3 months (or 12 weeks) on the ASD children. Each daily dosage of Zn was calculated as being equal to the body weight in kg plus 15–20 mg. The effect of Zn was also evaluated on the serum level of metallothionein 1 (MT-1A), and the severity of autism via scores on the Childhood Autism Rating Scale. The effect of Zn was investigated on the gene expression of MT1-A before and after Zn supplementation. The data of the present study showed an increase in cognitive-motor performance and an increased serum metallothionein concentration, as well as a significant lowering in the circulating serum levels of copper (Cu) following Zn supplementation. In the cohort of ASD patients, the genetic expression of MT-1 was higher after Zn therapy than before the treatment. In conclusion, Zn supplementation might be an important factor in the treatment of children with ASD.

Background The aim of the present study was to determine the type and percentage of referral situations, risk factors, associated syndromes, and parental awareness of autism spectrum disorder (ASD) children who visited the Medical Research Centre of Excellence, National Research Centre in Cairo, specialized in ASD diagnosis and management. Methods The study included 530 children who were diagnosed with ASD. For those, full medical history, clinical examination, severity evaluation, and testing the language and cognitive development were performed. The process of diagnosis and assessment of parents’ awareness and knowledge about ASD was investigated using questionnaires. Results The clinic was mainly visited by self-referral. About half of the participants (51.4 %) had previously visited other doctors (1–5 physicians) who were mostly pediatricians. The parents’ awareness was mostly limited to the term “autism”, but not the nature of ASD. Caesarean section was the most common risk factor (57.4 %), followed by jaundice (30.1 %). The most common presenting symptoms were language (81.5 %) and social (60.4 %) deficits. ASD severity was found to be high in association with attention deficit hyperactivity disorder (ADHD) and electroencephalogram (EEG) changes (p = 0.001). Conclusion The risk factors and associated syndromes in the Egyptian population studied were similar to those reported in previous studies performed in other populations, but their percentage was different. Perinatal problems were the most common risk factors, which may relate to the influence of gene-environmental interaction on the factors which could play a role in developing ASD or increasing its severity. The process of ASD diagnosis was commonly delayed among the participants. Increasing awareness and knowledge among health care professionals and parents is urgently needed to facilitate early diagnosis and intervention services, which will lead to improvement of the developmental outcomes for ASD children. The associated syndromes could be the driving force to seek medical advice and could influence the ASD severity.

En Abstract Introduction Microtia is a condition in which the external portion of the ear (the auricle) is malformed. In the strictest definition, there is also narrowing or absence of the external auditory canal (external auditory meatus). Microtia varies in severity from barely discernible to an external ear with major structural changes. Hearing loss is a common feature that can be associated with microtia. There are different types of hearing loss–conductive, sensorineural, or mixed–depending on which part of the ear is not working as it should. Objectives The present study was designed with the following aims: (i) identification of the genetic etiology and patterns of inheritance of microtia for proper genetic counseling; (ii) early detection and identification of associated hearing impairment for proper management including use of a hearing aid and surgical intervention. Patients and methods Twenty children with microtia ranging in age between 1 and 15 years (mean: 6.2 ± 3.68 years) irrespective of sex were included in this study: 14 males and six females. All children were subjected to a full assessment of medical history, a general examination, an ENT examination, tympanometry, pure tone audiometry, and an auditory steady-state response test for patients not responding to a conventional audiometric test. Karyotyping, fluorescence in-situ hybridization (FISH) for Treacher Collins cases, radiological investigations, and fundus examination were also performed. Results Syndromic microtia was more frequent than nonsyndromic microtia. Treacher Collins syndrome was the most clinically diagnosed syndrome, followed by Goldenhar’s syndrome. There was one case of Down’s syndrome and another single case of Johnson–McMillin syndrome. Meatal atresia and preauricular tags were frequently present in the microtia cases, whereas middle ear and inner ear anomalies were only found in some cases. The most common presenting symptom of microtia is hearing loss. Its degree and type differ according to the severity of the disease and frequencies affected. In total, 88.5% (23 ears) have conductive hearing loss and 11.5% (three ears) have mixed hearing loss. Karyotyping was performed for 10 cases; nine cases were normal, whereas one case was abnormal (47XY, +21) (Down’s syndrome), which represents 5% of all cases studied. FISH was performed for four cases of Treacher Collins syndrome using a probe for chromosome 5 with gene map locus 5q31q33, but no deletion was found in the chromosome 5 Treacher Collins–Franceschetti 1 (TCOF1) gene. Conclusion Genetic predisposition for both autosomal dominant and autosomal recessive inheritance seems to be a strong determinant factor in the etiology of microtia than the environmental one. As for Treacher Collins, which is the most frequently clinically diagnosed syndrome in the current study, the FISH study showed that the 5q31-q33 locus may not carry the causative mutation as no single case was positive for this locus. Hearing impairment, of the conductive type, is the most frequent symptom that leads parents to seek medical advice and genetic counseling.

Background Current estimates indicate that >80 % of children with autism spectrum disorder (ASD) exhibit concomitant sensory processing problems and hyper- or hypo-reactivity to sensory input. These are now included as diagnostic criteria for ASD in the Diagnostic and Statistical Manual of Mental Disorders—Fifth Edition. Chromosomal rearrangements, copy number variations (CNVs), and coding sequence variants involving >100 genes have been identified in patients with ASD. Studying the CNVs of one such gene, SHANK3, and the associated phenotype in patients with ASD could provide insights that will guide future ASD treatments and interventions. Objective To assess SHANK3 CNVs in children with ASD and investigate their sensory processing patterns using the Short Sensory Profile (SSP). Subjects and methods Forty children with ASD were assessed using the Autism Diagnostic Interview-Revised. SSP was used to evaluate atypical sensory behavior, e.g., hyper- or hypo-reactivity to sensory input or unusual sensory interests. SHANK3 CNVs were assessed in these children using Multiplex Ligation-dependent Probe Amplification. Results Of the 40 cases, 77.5 % showed sensory reactivity symptoms. The greatest difference from normality was observed in the under-responsive/seeks sensation domain, followed by the tactile sensitivity domain, whereas hypo-activity (low-energy/weak domain) was closest to normal. The sensory reactivity symptoms were significantly correlated with the severity of ASD. However, only three of the 40 cases had de novo duplications at 22q13.33. The duplications included SHANK3 in two of the cases and only the distal flanking region of SHANK3 in the third case. All three duplication cases also showed symptoms associated with the low-energy/weak domain. Conclusion We found that children with ASD exhibited sensory processing problems. The SHANK3 copy number gains found demonstrate the gene dosage effect of SHANK3 in ASD pathogenesis. This study adds to the growing understanding of 22q13 duplications that include SHANK3.

Autism spectrum disorders are complex developmental disorders with increasing incidence and poorly understood etiology. Imbalance of amino acids profoundly influences brain function, and is thought to be one of the key players in the pathophysiology of autism. This study aimed to measure the plasma amino acid profiles of 20 Egyptian and 20 Saudi autistic patients in comparison to matching healthy controls to clarify the role of impaired amino acid concentrations in the etiology of autism. Plasma amino acids profiles were measured using high performance liquid chromatography. While plasma levels of glutamic, aspartic, and glycine recorded the most significant percentage elevated amino acids, glutamine, asparagine, arginine, tyrosine and isoleucine recorded the most remarkable percentage decrease in autistic patients from both populations compared to controls. Among the calculated relative values, only acidic/basic, and glutamate/glutamine ratios were significantly higher in autistics compared to controls. Non-essential/essential and glucogenic/ketogenic ratios were unaltered in autistics compared to controls. Increased plasma glutamate/glutamine ratio, together with increased glycine, arginine, aspartate, aspargine levels, and acidic/basic amino acid ratio can serve as a predictive tools for the early detection of autism. These findings suggest that glu- tamatergic abnormalities in the brain may be associated with the pathobiology of autism.

AIM: In the hope to assist in tailoring individualized nutritional therapy, this study aimed to assess the nutritional status of autistic children.MATERIAL AND METHODS: This cross-sectional study included 80 autistic children, divided into two groups: group 1 (aged 3- 5 years) and group 2 (aged 6-9 years). Diagnosis was performed based on the criteria for autistic disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Autism Diagnostic Interview Revised and Autism Rating Scale.RESULTS: Socio-demographic data, anthropometric measurements and dietary intake patterns were recorded using a validated questionnaire. The daily intakes of calories and nutrients were converted to percentages of the Recommended Dietary Allowance or Dietary Reference Intake based on age- and gender-normalized DRIs. Plotting on the Egyptian sex-specific growth chart, BMI-z scores of both age groups were slightly overweight. Autistic children suffered inadequate intake of some micronutrients such as vitamin D and C, calcium, folate, magnesium, phosphorus, zinc, and iron, some deficiencies were highly significant especially at older age.CONCLUSIONS: Tailoring a specially designed balanced diet with appropriate micronutrient supplementation may ameliorate the severity of autism symptoms and related abnormal behaviours.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder afflicting about one in every 68 children. It is behaviorally diagnosed based on a triad of symptoms, including impairment in communication, impairment in sociability and abnormal and stereotypic behavior. The subjectivity of behavioral diagnosis urges the need for clinical biomarker tests to improve and complement ASD diagnosis and treatment. Over the past two decades, researchers garnered a broad range of biomarkers associated with ASD and often correlating with the severity of ASD, which includes metabolic and genetic biomarkers or neuroimaging abnormalities. Metabolic biomarkers are either involved in key pathways such as a trans-sulfuration pathway or produced due to the derangement of these pathways in the case of oxidative stress. Recent studies reported several genetic abnormalities related to ASD, encompassing various mechanisms, from copy number variations (CNVs) and single nucleotide polymorphisms (SNPs) to chromosomal anomalies. However, it is still premature to consider these genetic variants as true biomarkers for ASD, due to their low reproducibility and regional-specific nature. Herein, we comprehensively review state of the art about major biomarkers reported in ASD and the association of some biomarkers with ASD symptoms and severity. It is important to establish those biomarkers to be able to help in the diagnosis and to optimize the treatment of ASD.

Objectives: The verbal abilities of autistic children differ from those of typically developing ones and they also differ among autistic children themselves. Neuroanatomical changes and an abnormal organization of functional networks are expected to accompany such a neurodevelopmental disorder. The aim of this study was to delineate the brain neuroanatomical changes in Egyptian children with autism and to compare them with previous studies in order to add more insight into the global brain imaging deviations linked to autism. Patients and Methods: Twenty-five autistic children and 25 typically developing children underwent MRI. Further analysis was performed using surface-based morphometry to obtain cortical thickness, brain volume, and cortical complexity. Results: MRI analysis results revealed significantly greater cortical thickness, cortical complexity, and gray matter volume in the autistic as compared to the control group. On the other hand, the white matter volume was significantly smaller. Conclusion: These findings generally align with findings in previous studies, except for occasional differences.

Background Many risk factors interact together during the critical period of development and govern the future phenotype of autism spectrum disorder (ASD). Furthermore, co-occurring abnormalities among individuals with ASD vary a lot so as their abilities. Aim of work To investigate possible risk factors and to determine the prevalence of coexisting abnormalities in a sample of Egyptian ASD children and their influence on the severity and their communication performance. Methods The diagnosis and severity of ASD for participants (N = 80) was performed by DSM-5, ADIR and CARS. They were investigated regarding the possible risk factors and coexisting abnormalities. A detailed history taking, clinical examination, the Arabic preschool language scale, cognitive abilities assessment and other additional instrumental measures such as EEG were used. Results Caesarian section and neonatal jaundice were the most common risk factors. The severity of ASD was positively related to maternal and paternal ages. Developmental language disorder, intellectual disability, attention deficit hyperactivity disorder, sleep disorder and EEG changes were more frequently detected among studied cases. The CARS scores were significantly higher in ADHD and EEG changes groups. The most severely affected CARS items in the groups with these disorders were determined. Conclusion High parental ages has an impact on the severity of ASD. ADHD, sleep disorder, and EEG changes seem to have an impact on certain elements of the adaptive behavior especially the communicative performance of ASD individuals. We recommend to seriously investigate co-morbid abnormalities and consider them during the process of management of ASD for proper intervention plans.

The molecular basis of the pathophysiological role of oxidative stress in autism is understudied. Herein, we used polymerase chain reaction (PCR) array to analyze transcriptional pattern of 84 oxidative stress genes in peripheral blood mononuclear cell pools isolated from 32 autistic patients (16 mild/moderate and 16 severe) and 16 healthy subjects (each sample is a pool from 4 autistic patients or 4 controls). The PCR array data were further validated by quantitative real-time PCR in 80 autistic children (55 mild/moderate and 25 severe) and 60 healthy subjects. Our data revealed downregulation in GCLM, SOD2, NCF2, PRNP, and PTGS2 transcripts (1.5, 3.8, 1.2, 1.7, and 2.2, respectively; P < .05 for all) in autistic group compared with controls. In addition, TXN and FTH1 exhibited 1.4- and 1.7-fold downregulation, respectively, in severe autistic patients when compared with mild/moderate group ( P = .005 and .0008, respectively). This study helps in a better understanding of the underlying biology and related genetic factors of autism, and most importantly, it presents suggested candidate biomarkers for diagnosis and prognosis purposes as well as targets for therapeutic intervention.

Ring chromosomes are rare chromosomal disorders. Patients carrying a ring chromosome have different phenotypes depending on the degree of structural rearrangement. We observed an 8-year-old patient attending the clinic for autistic disorders. By cytogenetic analysis, we identified a de-novo ring chromosome 14. Our patient had a rare condition of developmental delay, behavioral hyperactivity, anxiety, and autistic traits in addition to severe drug-resistant epilepsy, indicating that these features might be part of a syndromic condition. In comparison with other ring 14 patients, the neurological features seen in this patient were extremely severe, in addition to having low-functioning autism. We believe that chromosome 14qter can have a role in the etiology of autism; therefore, cytogenetic analysis should be considered in autistic children.

The aim of this study was to assess the efficacy of an electronic treadmill exercise training programme on malondialdehyde (MDA) as a marker for lipid peroxidation and the antioxidant enzyme glutathione peroxidase (GPx) in adolescents with Down syndrome. The study was carried out on 30 adolescent males with Down syndrome, ranging in age from 15 to 18 years, with 30 healthy subjects as a control group. Clinical examination, anthropometric measurements and determination of GPx activity and MDA before and after exercise were done. A treadmill training programme was performed for 12 weeks. Our data showed a significant increase in GPx activity and decrease in serum level of MDA in Down syndrome individuals after treadmill exercise for 3 months. Exercise promotion for adolescents with Down syndrome requires attention to motivators and facilitators of exercise adherence as it may limit risk of increased neurological consequences associated with oxidative stress and improve quality of life.

Importance Autosomal recessive inherited neurodevelopmental disorders are highly heterogeneous, and many, possibly most, of the disease genes are still unknown. Objectives To promote the identification of disease genes through confirmation of previously described genes and presentation of novel candidates and provide an overview of the diagnostic yield of exome sequencing in consanguineous families. Design, Setting, and Participants Autozygosity mapping in families and exome sequencing of index patients were performed in 152 consanguineous families (the parents descended from a same ancestor) with at least 1 offspring with intellectual disability (ID). The study was conducted from July 1, 2008, to June 30, 2015, and data analysis was conducted from July 1, 2015, to August 31, 2016. Results Of the 152 consanguineous families enrolled, 1 child (in 45 families [29.6%]) or multiple children (107 families [70.4%]) had ID; additional features were present in 140 of the families (92.1%). The mean (SD) age of the children was 10.3 (9.0) years, and 171 of 297 (57.6%) were male. In 109 families (71.7%), potentially protein-disrupting and clinically relevant variants were identified. Of these, a clear clinical genetic diagnosis was made in 56 families (36.8%) owing to 57 (likely) pathogenic variants in 50 genes already established in neurodevelopmental disorders (46 autosomal recessive, 2 X-linked, and 2 de novo) or in 7 previously proposed recessive candidates. In 5 of these families, potentially treatable disorders were diagnosed (mutations in PAH , CBS , MTHFR , CYP27A1 , and HIBCH ), and in 1 family, 2 disease-causing homozygous variants in different genes were identified. In another 48 families (31.6%), 52 convincing recessive variants in candidate genes that were not previously reported in regard to neurodevelopmental disorders were identified. Of these, 14 were homozygous and truncating in GRM7 , STX1A , CCAR2 , EEF1D , GALNT2 , SLC44A1 , LRRIQ3 , AMZ2 , CLMN , SEC23IP , INIP , NARG2 , FAM234B , and TRAP1 . The diagnostic yield was higher in individuals with severe ID (35 of 77 [45.5%]), in multiplex families (42 of 107 [39.3%]), in patients with additional features (30 of 70 [42.9%]), and in those with remotely related parents (15 of 34 [44.1%]). Conclusions and Relevance Because of the high diagnostic yield of 36.8% and the possibility of identifying treatable diseases or the coexistence of several disease-causing variants, using exome sequencing as a first-line diagnostic approach in consanguineous families with neurodevelopmental disorders is recommended. Furthermore, the literature is enriched with 52 convincing candidate genes that are awaiting confirmation in independent families.

Although the etiology and pathology of autism spectrum disorder (ASD) is still poorly understood, a number of environmental, anthropological, neurobiological and genetic factors have been related to the pathophysiology of ASD, even the impact of oxidative stress response related to the environment and nutrition intake. Usual recommended dietary habits are based on the combination of behavioral and dietary or nutraceutical interventions together with pharmacotherapy. Investigations about a reliable relationship between diet and ASD are still lacking. The present study aimed at comparing dietary regimens and habits of normally developing apparently healthy children, without diagnosed ASD, with a pediatric population of individuals affected by autistic disorder. Assessments of nutritional and anthropometric data, in addition to biochemical evaluation for nutrient deficiencies, were performed. A total of 80 children with autistic disorder and 80 healthy, normally developing pediatric individuals were enrolled in the study. Parents were asked to complete the standardized questionnaire regarding the different types of food and the proportion of a serving for their children. Biochemical analysis of micro- and macronutrients were also done. Plotting on the Egyptian sex-specific anthropometric growth (auximetric) chart, absolute weights as well as weight-related for age classes, were significantly higher in cases than healthy controls. No differences between groups were observed in regard to total kilocalories (kcal), carbohydrates, and fat intake. A total of 23.8% of children with autistic disorder vs. 11.3% in the healthy control group had a nutrient intake with features below the Recommended Dietary Allowance (RDA) of protein. Children with autistic disorder showed low dietary intake of some micronutrients; calcium (Ca), magnesium (Mg), iron (Fe), selenium (Se) and sodium (Na), also they had significantly high intake of potassium (K) and vitamin C compared to healthy controls. Serum Mg, Fe, Ca, folate and vitamin B12 in children with autistic disorder were significantly low compared with healthy children. Significant positive correlations between serum Mg, Fe, Ca, vitamin B12 and folate and their levels in food were present. These results confirmed that different nutritional inadequacy was observed in Egyptian children with autistic disorder. The evidence reported in the present study should recommend screening of the nutritional status of ASD children for nutrient adequacy to reduce these deficiencies by dietary means or by administering appropriate vitamin and mineral supplements. Nutritional intervention plan should be tailored to address specific needs.

The autism phenotype is associated with an excess of brain volume due in part to decreased pruning during development. Here we aimed at assessing brain volume early in development to further elucidate previous findings in autism and determine whether this pattern is restricted to idiopathic autism or shared within the autistic phenotype (fragile X syndrome [FXS]). We investigated brain volume in 37 participants, using the fully automated Civet pipeline anatomical magnetic resonance imaging. 3 groups with intellectual deficiency: autism (AUT); its most associated FXS; and its most opposite Williams syndrome (WS) were compared with each other and with normal controls (NC). We report increased total and regional gray and white matter brain volume in AUT and FXS relative to WS and NC. These findings are discussed in light of the possibilities leading for the enlarged brain volume in children with the AUT phenotype. We speculate that this excess suggests reduced regression of neuronal processes “pruning” in cortical and subcortical regions in AUT/FXS, which may be due to a mutation in specific genes involved in pruning and/or a lack of socio-emotional environmental experience during a critical developmental period.

Aim: This study aimed at evaluation of MTHFR 677C/T and 1298A/C polymorphisms in MTHFR gene as maternal risk factors in conotruncal heart defects (CTDs). Material and Methods: Thirty cases with CTDs and their mothers and thirty control children and their mothers were studied. Medical and nutritional histories for all mothers were taken with emphasis on folate intake. The mutations in MTHFR gene are a C to T substitution at base pair 677 and a A to C at base pair1298 were investigated by polymerase-chain reaction, followed by restriction enzyme digestion and detection by electrophoresis. Results: Folic acid intake was below the recommended daily allowance in case mothers compared to control mothers. No significant difference between patients and control group or their mothers regarding MTHFR gene polymorphisms at exon 4. Significant difference between case and control groups and between their mothers regarding MTHFR gene polymorphisms at exon 7. Homozygous genotype frequencies of MTHFR at position 1298 was significantly higher in cases and their mothers with an odds ratio 56 (95% confidence interval 10.3-303.7). Conclusion: Egyptian population may have high incidence of MTHFR polymorphism at exon 7 rather than at exon 4. Preconception folate intake might decrease MTHFR polymorphism at exon 7 and decrease risk of CTD.

Background Genetically Williams syndrome (WS) promises to provide essential insight into the pathophysiology of cortical development because its ∼28 deleted genes are crucial for cortical neuronal migration and maturation. Phenotypically, WS is one of the most puzzling childhood neurodevelopmental disorders affecting most intellectual deficiencies (i.e. low-moderate intelligence quotient, visuospatial deficits) yet relatively preserving what is uniquely human (i.e. language and social-emotional cognition). Therefore, WS provides a privileged setting for investigating the relationship between genes, brain and the consequent complex human behaviour. Methods We used in vivo anatomical magnetic resonance imaging analysing cortical surface-based morphometry, (i.e. surface area , cortical volume , cortical thickness , gyrification index ) and cortical complexity , which is of particular relevance to the WS genotype–phenotype relationship in 22 children (2.27–14.6 years) to compare whole hemisphere and lobar surface-based morphometry between WS (n = 10) and gender/age matched normal controls healthy controls (n = 12). Results Compared to healthy controls, WS children had a (1) relatively preserved Cth; (2) significantly reduced SA and CV; (3) significantly increased GI mostly in the parietal lobe; and (4) decreased CC specifically in the frontal and parietal lobes. Conclusion Our findings are then discussed with reference to the Rakic radial-unit hypothesis of cortical development, arguing that WS gene deletions may spare Cth yet affecting the number of founder cells/columns/radial units, hence decreasing the SA and CV. In essence, cortical brain structure in WS may be shaped by gene-dosage abnormalities.

Background: Autism is among the commonest neurodevelopmental childhood disorders worldwide; its aetiology is still unknown. Iron metabolism alteration in the central nervous system is recently implicated as a risk factor for several neurodegenerative disorders.Haemochromatosis HFE gene polymorphisms (p.H63D and p.C282Y) have shown significant association with several neurological diseases. Some evidences show altered iron related proteins in serum of autistic children. The aim of this work is to conduct a preliminary pilot study for the association of HFE polymorphisms and autism.Methods: All cases were referred from the clinic of special needs, National Research Centre, Cairo. Clinical diagnosis was based on the criteria for autistic disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR).Whole genome DNA was extracted; p.H63D and p.C282Y genotyping was studied using specific sequence amplification followed by restriction enzyme digestion on a sample of autism patients (25 cases) and twenty controls.Results: The p.H63D is more abundant than the C282Y among both autism and control samples. No significant association of p.H63D nor p.C282Y polymorphism and autism was revealed.Conclusion: We here report on the first pilot study of the possible genetic association between autism and HFE gene polymorphisms among Egyptians. Although our results do not prove the role of HFE polymorphisms as risk factors for autism, yet this does not exclude the role of iron in this prevalent disorder. Further extended studies are recommended to include other iron metabolism genes.

Down syndrome (DS) is the phenotypic manifestation of trisomy 21. Our study was concerned with the characterization and purification of glutathione S-transferase enzyme (GST) from normal and Down syndrome (DS) erythrocytes to illustrate the difference in the role of this enzyme in the cell. Glutathione S-transferase and glutathione (GSH) was determined in ten DS and ten healthy children matched for age (3-10 years). DS group exhibited significantly lower GST value (2.7 units/gHb) as compared to controls (6.6 units/gHb) (40.9%). GST activity was significantly decreased to 40.9% in the DS group as compared to controls. Also GSH concentration was significantly decreased to 60.6% in the DS group compared to the controls. Glutathione transferase was purified from erythrocytes of normal and DS pooled blood samples by affinity chromatography with specific activity of 23.7% and 7.9%, respectively. The effect of freezing and thawing, storage time of freezing and GSH concentration on the stability of the enzyme were examined. Normal GST exhibited a pH optimum at pH 7 followed by sharp decrease, however DS GST exhibited pH optimum between pH 7.5 and 8. The Km values for 1-chloro-2,4-dinitrobenzene (CDNB) and GSH were 0.205 mM and 0.786 mM, respectively, for normal GST, and 0.318 mM and 1.307 mM, respectively for DS GST. The activation energy (Ea) was calculated to be 2.25 and 4.25 cal/mol for normal GST and 3.8 cal/mol for DS GST. Normal and DS GST were inhibited by the same inhibitors (hematin, bromosulfophthalein and cibacron blue), but with different degree. On kinetic basis, the individuals with lower overall GST activity and slight differences in some kinetic characters are at greater risk from xenobiotic contamination as compared to those with higher overall GST activity observed in normal individuals.

Objective To assess homocysteine, folic acid and vitamin B 12 , trace element levels and oxidant/antioxidant status in Down syndrome (DS) mothers and children. Design and methods 42 mothers with previous history of bearing DS baby with karyotypically confirmed full trisomy 21 were included. 48 healthy mothers with their healthy children were considered as control. Serum B 12 , folic acid, total homocysteine (tHcy), vitamins E and C, TBARS and trace elements were estimated. Results DS mothers showed higher levels of tHCy, lower levels of folic acid and vitamin B 12 than controls. tHCy and folic acid concentrations were significantly decreased, while vitamin B 12 exhibited a slight decrease in DS children versus control. Vitamins E and C, zinc and copper levels were markedly reduced in DS mothers. By contrast, TBARS showed significant elevation in them. Furthermore, DS children had severe reduction of vitamin C and zinc levels relative to healthy children. However, vitamin E showed slight reduction and TBARS displayed a slight rise in DS children. Conclusion Abnormal folic acid-homocysteine metabolism is a potent marker to identify women at risk for having DS child and it also exposes them to oxidant/antioxidant imbalance.

Objective Estimation of free polyunsaturated fatty acids (PUFAs) in blood and evaluation of behavior of autistic children before and after taking fish oil (Efalex®) were performed. Design and methods 30 autistic children (18 males and 12 females) aged 3–11 years and 30 healthy children as control group were included in this study. Tandem mass spectrometry and CARS were used to estimate the free PUFAs from dried blood spot and to evaluate the autistic behavior respectively. Results Before taking Efalex®, linolenic acid showed a significant reduction (71%), followed by docosahexaenoic acid (65%) and arachidonic acid (45%), while linoleic acid was the least affected PUFA (32%). After taking Efalex®, 66% of autistic children showed clinical and biochemical improvement, linolenic acid and docosahexaenoic acid showed the highest levels after Efalex® supplementation. Conclusion PUFA supplementation may play an important role in ameliorating the autistic behavior.