Healthy Control Children Research Articles

Frequency of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in peripheral blood of pediatric patients with SARS CoV-2 Infection: a pilot study

Background: Cytokine storm has been observed in some patients with SARS-CoV-2 due to excessive pro-inflammatory response. Foxp3(+) regulatory T cells (Tregs) are a distinct population of CD4(+) lymphocytes identified by their expression of transcription factor forkhead homeobox protein-3 (Foxp3). These cells down-regulate immune responses in inflammatory and autoimmune diseases. Objective: This pilot study was aimed to investigate the levels of CD4(+)CD25(+)Foxp3(+) Tregs in children with SARS-CoV-2. Methods: frequency of Tregs was measured by flow cytometry in 20 patients with SARS-CoV-2, 6 months to 15 years old;6 had COVID-19 and 14 had multisystem inflammatory syndrome in children (MIS-C). They were compared to 20 age-and sex-matched healthy children as a control group. Results: There was no significant difference between patients with SARS-CoV-2 infection and healthy control children in the frequency of Tregs (P=0.068). Decreased numbers of Tregs was found in only 10% of SARS-CoV-2 patients. Patients with severe SARS-CoV-2 were comparable to those with moderate disease in terms of Tregs' levels. The frequency of Tregs correlated negatively with neutrophil counts in our series (p=0.036). Attempts of correlation with other inflammatory markers of SARS-CoV-2 were insignificant. Conclusion: Decreased levels of Tregs were found in only 10% of our SARS-CoV-2 infected children. The frequency did not correlate with the disease severity or levels of routine inflammatory markers of SARS-CoV-2. Thus, Tregs expression does not seem to have a role in the up-regulated immune response seen in moderate and severe SARS-CoV-2 infection. Our conclusions are limited by the sample size.

Interleukin 10 -1082 G/A Gene Polymorphism and Susceptibility to Bronchial Asthma in Children: A Single-Center Study.

Interleukin-10 (IL-10) is the key regulator of immune responses preventing the undesirable exaggerated ones. Genetic variation in the promoter region of IL-10 may influence its serum level and contribute to susceptibility to bronchial asthma in children. This is a case-control study including 100 patients and 100 healthy control children who had undergone skin prick test, estimation of total IgE and serum level of IL-10 by enzyme-linked immunosorbent assay, and polymerase chain reaction-restriction fragment length polymorphism for IL-10 gene polymorphism. A significant association between IL-10 polymorphism and susceptibility to pediatric asthma was found. AA genotype represented (66%) of the patient group compared to (6%) only of the control group, while AG genotype was detected in 20% of patients and 4% of control. In contrast, wild genotype GG was found in 14% of patients and 90% of control with a highly statistically significant difference among both groups (P < 0.001). The serum level of IL-10 was significantly elevated in the GG genotype in comparison to other genotypes (P < 0.001), and it was negatively correlated with the severity of asthma among the studied pediatric asthmatic group (P < 0.001). In conclusion, IL-10 polymorphism may play an important role in the development of bronchial asthma in children.

Effect of textured foot orthoses on walking plantar pressure variables in children with autism spectrum disorders

The aim of this study was to evaluate the effect of textured foot orthoses on plantar pressure variables in children with autism spectrum disorders (ASDs). Thirty boys were divided into two groups based on their health status, namely: autism spectrum disorder and healthy matched controls. Plantar pressure data were captured during stance phases of shod walking with and without textured foot orthoses. Remarkably larger peak force under the toe1 and metatarsal1 and peak pressure under the toe1 and toe2-5 regions were observed in the autism group comparing with the healthy group, while lower peak force under the toe1, metatarsal1 and metatarsal2 were seen during walking with textured foot orthoses comparing with the cases of walking without them. The results showed higher values of peak pressure under metatarsal3, metatarsal4 and metatarsal5 for the textured foot orthoses walking against the cases without them. Also, analysis depicted huge reductions from pre-to-posttest for the peak pressure under toe2-5 only cases within the autism group. The reason of observing higher peak values of forces and pressures within their forefoot can potentially be their tendency to walk on their toes comparing against the healthy control children. This causes lower pressure values within all toes and the first metatarsal regions during normal walking with textured foot orthoses than walking without them. The findings revealed that the use of textured foot orthoses reduced peak pressure under toe2-5 only in the autism group. This suggests that the use of such interventions can help boys with ASDs move more safely.

Serum Periostin Predicts Wheezing Exacerbation: A Prospective Study in Preschool Children with Recurrent Wheezing

Introduction: Wheezing is a common problem in preschool children. Currently, there are no reliable biomarkers that can predict subsequent wheezing in preschool children. This study aimed to compare serum periostin levels between preschool children with and without recurrent wheezing and investigate its utility for predicting acute wheezing exacerbation. Methods: Children aged 2–5 years with recurrent wheezing and healthy control children were enrolled. They were evaluated for serum periostin level at enrollment and subsequently followed for wheezing episodes in a 1-year prospective study. Results: A total of 122 children were enrolled. Children in the recurrent wheezing group (n = 80) had a greater median serum periostin level (1,122.32 pg/mL [<10–6,978.93]) than that of the healthy control group (n = 40) (<10 pg/mL [<10–2,116.69]), p value = 0.006. After 1-year follow-up, subjects who experienced subsequent wheezing exacerbation episodes had a greater median of periostin level (5,321 pg/mL) compared with those with no exacerbation (<10 pg/mL), p value = 0.014. ROC curve analysis revealed that the level of serum periostin >1,200 pg/mL, corresponding to 78.9% sensitivity and 64.6% specificity, with an AUC of 0.701, p value = 0.009, could be a predictor for acute wheezing exacerbation within 1 year. Besides, subjects with serum periostin >1,200 pg/mL had greater odds of subsequent wheezing episodes compared with those with lower levels of serum periostin (adjusted odds ratio 10.0, 95% confidence interval: 2.3–43.5). Conclusions: Preschool children with recurrent wheezing have a greater serum periostin level than healthy control. Serum periostin may be a valuable biomarker for predicting acute wheezing exacerbations in the following year.

Myostatin serum levels in children with type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) can cause several complications, among them myopathy, which can appear even in adolescents. This is of importance, since skeletal muscle is the largest of the insulin-sensitive tissues and thus plays a significant role in glucose homeostasis. A prime regulator of skeletal muscle mass is myostatin, a protein which has a negative role in skeletal muscle development but also in glucose homeostasis, causing insulin resistance. Since myopathy is a complication of T1DM and myostatin is a fundamental regulator of skeletal muscle and is also involved in glucose homeostasis, we investigated the serum levels of myostatin in children with T1DM. We determined myostatin serum levels using ELISA in 87 children with T1DM aged 10.62 ± 3.94years, and in 75 healthy children aged 10.46 ± 3.32years old. Myοstatin was significantly elevated in T1DM compared to the healthy control children (23.60 ± 7.70 vs 16.74 ± 6.95ng/ml, p < 0.0001). Myostatin was not correlated with body mass index (BMI) SD or hemoglobin A1c (HbA1c). Children with T1DM have significantly higher serum levels of myostatin compared to healthy children of the same age and BMI SD. The elevated myostatin in T1DM could reflect impaired muscle function and/or glucose metabolism, or could represent a homeostatic mechanism.

Instrumented classification of patients with early onset ataxia or developmental coordination disorder and healthy control children combining information from three upper limb SARA tests.

Early Onset Ataxia (EOA) and Developmental Coordination Disorder (DCD) share several phenotypical characteristics, which can be clinically hard to distinguish. To combine quantified movement information from three tests obtained from inertial measurements units (IMUs), to improve the classification of EOA and DCD patients and healthy controls compared to using a single test. Using IMUs attached to the upper limbs, we collected data from EOA, DCD and healthy control children while they performed the three upper limb tests (finger to nose, finger chasing and fast alternating movements) from the Scale for the Assessment and Rating of Ataxia (SARA) test. The most relevant features for classification were extracted. A random forest classifier with 300 trees was used for classification. The area under the receiver operating curve (ROC-AUC) and precision-recall plots were used for classification performance assessment. The most relevant discerning features concerned smoothness and velocity of movements. Classification accuracy on group level was 85.6% for EOA, 63.5% for DCD and 91.2% for healthy control children. In comparison, using only the finger to nose test for classification 73.7% of EOA and 53.4% of DCD patients and 87.2% of healthy controls were accurately classified. For the ROC/precision recall plots the AUC was 0.96/0.89 for EOA, 0.92/0.81 for DCD and 0.97/0.94 for healthy control children. Using quantified movement information from all three SARA-kinetic upper limb tests improved the classification of all diagnostic groups, and in particular of the DCD group compared to using only the finger to nose test.

IL-23/Th17 pathway and IL-17A gene polymorphism in Egyptian children with immune thrombocytopenic purpura

BackgroundImmune thrombocytopenic purpura (ITP) is an acquired complex autoimmune thrombocytopenia. Uncontrolled cellular immune response is one of the key triggers for the loss of immune tolerance in ITP patients. The purpose of this study was to investigate the association of IL-23/Th17, IL-17A and IL-17A rs2275913 gene polymorphism with ITP in Egyptian children.Methods60 patients with ITP and 50 healthy control children from Minia city- Egypt were involved. Serum levels of IL-23 and IL-17A were determined by enzyme-linked immunosorbent assay. The frequency of Th17 cells was measured using flow cytometer. Genotyping for IL-17A was performed via polymerase chain reaction-restriction fragment length polymorphism.ResultsComparing children with ITP to controls, serum levels of IL-23 and IL-17A as well as Th17 cells percentage were significantly increased (p < 0.001). Also, higher levels of these ILs and Th17 cells percentage were associated with decreased platelet count within ITP patients (p < 0.001). Analysis of genotype frequencies for IL-17A rs2275913 polymorphism and its alleles (A, G) showed no significant difference between cases and controls. Likewise, no significant differences were demonstrated between acute and chronic ITP regarding both IL-17A rs2275913 polymorphism prevalence and levels of IL-23, IL-17A plus Th17 cells percentage. The frequency of A alleles was 85 and 86% within patients and controls, respectively.ConclusionsElevated levels of IL-23, IL-17A and Th17 cells may be involved in ITP pathogenesis while IL-17A polymorphism rs2275913 is not prevalent in Egyptian children with ITP.

Is There a Difference between the Preoperative and Postoperative Serum Levels of Interleukin-6 and Tumor Necrosis Factor-α in Children Submitted to Adenotonsillectomy?

Introduction Palatine and pharyngeal tonsils are the first line of defense against pathogens. Clinically, two alterations may require surgical removal of the tonsils: hypertrophy and recurrent tonsillitis. The two conditions probably result from a dysfunction of the immune system. Objective To evaluate possible differences in the plasma levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in patients submitted to adenotonsillectomy. Methods Prospective, longitudinal study with 25 children undergoing adenotonsillectomy separated into 3 different groups: recurrent tonsillitis (RT), composed of 7 patients; recurrent hypertrophy tonsillitis (RTTH), with 8 patients; and the tonsillar hypertrophy (TH) group, with 10 patients. Ten healthy control children (SD) were also included in the study. Peripheral blood was collected, and plasma was separated to measure the levels of TNF-α, IL-6, and IL-10. The Mann-Whitney test was used for statistical analysis. Results The plasma level of IL-6 was higher in the RT ( p = 0.0394) and TH ( p = 0.0009) groups, compared with the control group. The TH group also had higher levels of IL-6 than the RT group ( p = 0.039). The IL-6/IL-10 ratio was higher in the RT ( p = 0.029) and TH ( p = 0.0005) groups compared with the control group. Between the RT and RTTH groups, the IL-6/IL-10 ratio was higher in the RT group, with a statistically significant difference ( p = 0.0091). Conclusion Patients with a history of chronic tonsillitis had higher levels of IL-6, compared with the control group.

Urine metabolic phenotyping in children with nocturnal enuresis and comorbid neurobehavioral disorders

Nocturnal enuresis (NE) is a common problem among 10% school-aged children. The etiologies underlying childhood NE is complex and not fully understood nowadays. Nevertheless, increasing evidence suggests a potential link between neurobehavioral disorders and enuresis in children. In this study, we aimed to explore novel metabolomic insights into the pathophysiology of NE and also, its association with pediatric psychiatric problems. Urine collected from 41 bedwetting children and 27 healthy control children was analyzed by using 1H-nuclear magnetic resonance spectroscopy from August 2017 to December 2018. At regular follow-up, there were 14 children with refractory NE having a diagnosis of attention deficient hyperactivity disorder (ADHD) or anxiety. Eventually, we identified eight significantly differential urinary metabolites and particularly increased urinary excretion of betaine, creatine and guanidinoacetate linked to glycine, serine and threonine metabolism were associated with a comorbidity of neurobehavioral disorders in refractory bedwetting children. Notably, based on physiological functions of betaine acting as a renal osmolyte and methyl group donor, we speculated its potential role in modulation of renal and/or central circadian clock systems, becoming a useful urinary metabolic marker in diagnosis of treatment-resistant NE in children affected by these two disorders.

Favorable antibody responses to human coronaviruses in children and adolescents with autoimmune rheumatic diseases

BackgroundDifferences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), between children and adults remain unexplained, and the effect of underlying immune dysfunction or suppression is unknown. Here, we sought to examine the antibody immune competence of children and adolescents with prevalent inflammatory rheumatic diseases, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), and juvenile systemic lupus erythematosus (JSLE) against the seasonal human coronavirus (HCoV)-OC43 that frequently infects this age group.MethodsSera were collected from JIA (n = 118), JDM (n = 49), and JSLE (n = 30) patients and from healthy control (n = 54) children and adolescents prior to the coronavirus disease 19 (COVID-19) pandemic. We used sensitive flow-cytometry-based assays to determine titers of antibodies that reacted with the spike and nucleoprotein of HCoV-OC43 and cross-reacted with the spike and nucleoprotein of SARS-CoV-2, and we compared them with respective titers in sera from patients with multisystem inflammatory syndrome in children and adolescents (MIS-C).FindingsDespite immune dysfunction and immunosuppressive treatment, JIA, JDM, and JSLE patients maintained comparable or stronger humoral responses than healthier peers, which was dominated by immunoglobulin G (IgG) antibodies to HCoV-OC43 spike, and harbored IgG antibodies that cross-reacted with SARS-CoV-2 spike. In contrast, responses to HCoV-OC43 and SARS-CoV-2 nucleoproteins exhibited delayed age-dependent class-switching and were not elevated in JIA, JDM, and JSLE patients, which argues against increased exposure.ConclusionsConsequently, autoimmune rheumatic diseases and their treatment were associated with a favorable ratio of spike to nucleoprotein antibodies.FundingThis work was supported by a Centre of Excellence Centre for Adolescent Rheumatology Versus Arthritis grant, 21593, UKRI funding reference MR/R013926/1, the Great Ormond Street Children’s Charity, Cure JM Foundation, Myositis UK, Lupus UK, and the NIHR Biomedical Research Centres at GOSH and UCLH. This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK, the UK Medical Research Council, and the Wellcome Trust.

Serum decoy receptor 3 (DcR3): a promising biomarker for atopic asthma in children.

Bronchial asthma is a common chronic inflammatory disease with high prevalence and morbidity, particularly in school-aged children. Decoy receptor 3 (DcR3) is a soluble decoy receptor that belongs to the tumor necrosis factor receptor superfamily and has been reported to be elevated in several allergic and inflammatory diseases. This study was designed to determine the role of DcR3 in pediatric asthma. The serum DcR3 levels were analyzed in 85 subjects (60 pediatric patients with bronchial asthma and 25 age- and sex-matched healthy control children) using the enzyme-linked immunosorbent assay technique. Patients with asthma had higher serum DcR3 levels than healthy control subjects (p = 0.007). In the atopic group of patients with asthma, the serum DcR3 levels were inversely correlated with the asthma control test score (R = - 0.392, p = 0.039). Overall, DcR3 could be a promising biomarker of atopic asthma, specifically in pediatric patients.

P–583 Differential lipidomic characteristics of children born to women with polycystic ovary syndrome

Abstract Study question To describe lipidomic characteristics of offspring born to polycystic ovary syndrome (PCOS-off) women and assess the associations of clinical phenotypes changes with differential lipids. Summary answer PCOS-off showed specific changes in lipidomics and some differential lipids (e.g., phosphatidylcholines, lysophosphatidylcholine and sphingomyelin) may be the potential markers of aberrant cardiometabolic health. What is known already Polycystic ovary syndrome (PCOS), the most prevalent endocrine disorder characterized by ovulatory dysfunction, hyperandrogenism and polycystic ovarian morphology, affects about 8–13% of women of fertile age. Aberrant metabolic pathophysiological changes and increased pregnancy complications associated with PCOS predispose PCOS patients to have suboptimal intrauterine environments and that may produce a detrimental impact on the cardiometabolic health of their children. Study design, size, duration A total of 141 blood plasma samples from 70 children born to PCOS women (43 girls, 27 boys) and 71 healthy control children (44 girls, 27 boys) were obtained for lipidomics. Participants/materials, setting, methods Blood samples were centrifuged at 2000 rpm, 4 °C for 20 min, and the upper plasma was collected and used for lipid extraction. Then the waters ACQUITY UPLC I-Class system and The Xevo G2-S Q-TOF with an electrospray ionization (ESI) source (Waters, Manchester, UK) was used for chromatographic analysis and mass spectrometry analysis separately. Main results and the role of chance In total, 44 metabolites were found to be significantly altered in PCOS-off, including 8 up-regulated and 36 down-regulated metabolites. After stratified by sex, 44 metabolites were found to express differently in girls born to PCOS women (PCOS-g). 13 metabolites were up-regulated, and 31 metabolites were down-regulated, most of which belong to glycerolipids species. While 46 metabolites were found to express differently in boys born to PCOS women (PCOS-b) with 9 increased metabolites and 35 decreased ones, most of which were glycerophospholipids metabolites. Additionally, significant associations between metabolites changes and weight Z-score as well as high density lipoprotein level were found in PCOS-off. In PCOS-g, triglyceride, low density lipoprotein and high density lipoprotein level were found to be correlated with some metabolites, whereas in PCOS-b, thyroid stimulating hormone and high density lipoprotein were correlated with some lipids. Limitations, reasons for caution Other species of metabolites except lipids are not included in this study. Besides, some potential confounding maternal factors, such as smoking, drinking, breastfeeding etc. were not included due to the lack of data. Wider implications of the findings: The results had broadened our understanding of PCOS-off’s cardiometabolic status and emphasized monitor and special management in this susceptible group of population. Trial registration number Not applicable

Cortical Morphometric Abnormality and Its Association with Working Memory in Children with Attention-Deficit/Hyperactivity Disorder.

ObjectiveAttention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adolescents. The present study investigated the cortical morphology features and their relationship with working memory (WM). Methods In the present study, a total of 36 medication naïve children with ADHD (aged from 8 to 15 years) and 36 age- and gender-matched healthy control (HC) children were included. The digit span test was used to evaluate WM. The magnetic resonance imaging (MRI) was used to examine the characteristics of cortical morphology. Firstly, we compared the cortical morphology features between two groups to identify the potential structural alterations of cortical volume, surface, thickness, and curvature in children with ADHD. Then, the correlation between the brain structural abnormalities and WM was further explored in children with ADHD. Results Compared with the HC children, the children with ADHD showed reduced cortical volumes in the left lateral superior temporal gyrus (STG) (p=6.67×10-6) and left anterior cingulate cortex (ACC) (p=3.88×10-6). In addition, the cortical volume of left lateral STG was positively correlated with WM (r=0.36, p=0.029). Conclusion Though preliminary, these findings suggest that the reduced cortical volumes of left lateral STG may contribute to the pathogenesis of ADHD and correlate with WM in children with ADHD.

CHARGE syndrome and related disorders: a mechanistic link.

CHARGE syndrome is an autosomal dominant malformation disorder caused by pathogenic variants in the chromatin remodeler CHD7. Affected are craniofacial structures, cranial nerves and multiple organ systems. Depending on the combination of malformations present, its distinction from other congenital disorders can be challenging. To gain a better insight into the regulatory disturbances in CHARGE syndrome, we performed RNA-Seq analysis on blood samples of 19 children with CHARGE syndrome and a confirmed disease-causing CHD7 variant in comparison with healthy control children. Our analysis revealed a distinct CHARGE syndrome pattern with downregulation of genes that are linked to disorders described to mimic the CHARGE phenotype, i.e. KMT2D and KDM6A (Kabuki syndrome), EP300 and CREBBP (Rubinstein-Taybi syndrome) and ARID1A and ARID1B (Coffin-Siris syndrome). Furthermore, by performing protein-protein interaction studies using co-immunoprecipitation, direct yeast-two hybrid and in situ proximity ligation assays, we could demonstrate an interplay between CHD7, KMT2D, KDM6A and EP300. In summary, our data demonstrate a mechanistic and regulatory link between the developmental disorders CHARGE-, Kabuki- and Rubinstein Taybi-syndrome providing an explanation for the overlapping phenotypes.

Serum Vitamin D Levels and the Risk of Pneumonia in Children

This systematic review and meta-analysis aimed to evaluate the association between serum vitamin D concentrations and the risk of pneumonia in children. Human studies reporting serum vitamin D levels in children with pneumonia and healthy controls were collected from different databases. The standardized mean difference and 95% confidence interval were calculated to evaluate the relationship between risk incidence of pneumonia and serum vitamin D levels. The results of analysis showed that serum vitamin D levels in children with pneumonia were significantly lower than those in healthy control children.

A case control study on role of zinc levels in acute lower respiratory infections

Pediatric respiratory disease remains an important cause of morbidity in both the developing and the developed world. It has become the most common reason parents cite for taking their children to see the general practitioner, and nutritional factors are a major reasons for ALRI. Objective: Acute respiratory infection is a leading cause of morbidity and mortality in fewer than five children worldwide especially in developing countries. Hence, the present study was undertaken to identify the serum zinc level in children’s hospitalized with acute lower respiratory tract infections (ALRI) in children aged 6 months to 5 yr. Methods: 100 cases fulfilling WHO criteria for pneumonia, in the age group 6 months to 5 yr were interrogated for potential nutritional risk factors as per a predesigned proforma and serum zinc level was measured. 100 healthy control children in the same age group were also interrogated and zinc level measured. Results: Significant low serum zinc level (p value

Association of cytotoxic T lymphocyte 4 gene with auto-antibodies in children with type 1 diabetes

Objective The aim of the study was to detect the association of CTLA4 gene with anti-insulin antibodies in type 1 diabetes in children. Background The objective was to evaluate the diagnostic workup done for diabetic children in its relation to clinical findings and diabetic control, and to study association of CTLA4 gene and anti-insulin antibodies in type 1 diabetes in children. Materials and methods The results showed no significant difference between male and females regarding serum anti-insulin antibodies and CTLA4 gene. There was a significant positive correlation between serum anti-insulin antibody and duration of disease of type 1 diabetes, but there was an insignificant association between CTLA4 gene and anti-insulin antibodies and type 1 diabetes. Results The study was carried out in the Pediatric Endocrinology and Genetic Units in Menoufia University Hospital and Damnhour Medical Institute. One hundred children with type 1 diabetes were enrolled (44 males and 56 females). Their age ranged from 2 to 17 years, with a mean of 9.3 ± 13.6 years. Data were collected including detailed history and thorough clinical examination, including anthropometric measures (body weight, standing height, BMI, and laboratory data). Assessments of serum anti-insulin antibodies and CTLA4 gene were done for all cases and for 100 apparently healthy control children (51 males and 49 females), whose age ranged from 3 to 16, with mean of 8.45 ± 3.48 years. Conclusion This study concluded that serum anti-insulin antibodies can be used as a marker in diagnosis of new cases of type 1 diabetes in children.

Plasma levels of nerve growth factor in Egyptian autistic children: Relation to hyperserotonemia and autoimmunity

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.

Serum Chitotriosidase level as a Novel Biomarker for Therapeutic Monitoring of Nephropathic Cystinosis among the Iraqi children

Background: Cystinosis is a rare autosomal recessive lysosomal storage disease with high morbidity and mortality. It is caused by mutations in the CTNS gene that encodes the cystine transporter, cystinosin, which leads to lysosomal cystine accumulation. It is the major cause of inherited Fanconi syndrome, and should be suspected in young children with failure to thrive and signs of renal proximal tubular damage. The diagnosis can be missed in infants, because not all signs of renal Fanconi syndrome are present during the first months of life. Elevated white blood cell cystine content is the cornerstone of the diagnosis. Since chitotriosidase (CHIT1 or chitinase-1) is mainly produced by activated macrophages both in normal and inflammatory conditions which suggest that cystinosis should be included within the differential diagnosis of disorders associated with increased plasma chitotriosidase activity. This study is aimed to estimate serum chitotriosidase level, as a screening marker and therapeutic monitor for cystinosis disease in Iraqi children with cystinosis.Subjects and Methods: The present study is a case-control study that included samples of 30 children with nephropathic cystinosis, compared to 25 healthy control children from those attending at The Genetic Rare Diseases Center / AL-Emamain AL-Kadhimain Teaching Hospital, Baghdad-Iraq.Results: Our results reported that cystinotic children had a marked elevation of serum chitotriosidase activity, compared to age-matched healthy children, besides a significant associated with leukocyte-cystine content for cystinotic patients.CHT1 as a Novel BiomarkerConclusion: Estimation of serum chitotriosidase activity might aid in monitoring the therapeutic benefits of cysteamine therapy, as well as the prognosis of the disease when WBC cystine assessment is not available.Key Words: Cystinosis, Cysteamine, Chitotriosidase.

Effect of DRD4 Receptor -616 C/G Polymorphism on Thalamic GABA Levels in Pediatric Patients With Primary Nocturnal Enuresis.

The single nucleotide polymorphism (SNP) of dopamine D4 receptor (DRD4) promoter (-616; rs747302) is associated with abnormalities of the thalamus in children suffering from primary nocturnal enuresis (PNE). To investigate the effect of DRD4 -616 C/G SNP on thalamic gamma-aminobutyric acid (GABA) levels in PNE children. Prospective, observational. One hundred and seventy-six children with PNE and 161 healthy control children. 3 T, three-dimensional T1-weighted turbo field echo sequence and MEscher-Garwood Point RESolved Spectroscopy (MEGA-PRESS) MRS sequence. The MEGA-PRESS MRS sequence was used to measure thalamic GABA spectra. The thalamic GABA+ level was calculated using the Gannet 3.0 software package for each participant. A questionnaire was used to determine arousal from sleep (AS) scores. Comparisons of the AS scores and thalamic GABA+ levels were performed using the Mann-Whitney U test between C-allele carriers and GG homozygotes in the PNE and control groups. Spearman correlation analysis was performed to determine the association between AS scores and thalamic GABA levels in PNE children. Thalamic GABA levels in the PNE group were significantly higher than those in the healthy control group (0.178 (0.169-0.186) vs. 0.154 (0.146-0.164), Z=8.526, Pcorrected < 0.001). The GABA levels in C-allele carriers were significantly higher than those in GG homozygotes in both the PNE and control groups (0.184 (0.181-0.193) vs. 0.170 (0.165-0.177), Z=8.683, Pcorrected < 0.001; 0.166 (0.156-0.170) vs. 0.147 (0.141-0.152), Z=9.445, Pcorrected < 0.001). GABA levels in the thalamus were also significantly and positively correlated with AS scores in C-allele carriers in the PNE group (r=0.747, P < 0.05). DRD4 -616 C allele may be associated with increased thalamic GABA+ levels, especially in C-allele carrying PNE children. 2 TECHNICAL EFFICACY STAGE: 3.